Teses / dissertações sobre o tema "Transport intracellulaire des protéines"
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Fayadat, Laurence. "Maturation et transport intracellulaire de la thyropéroxydase humaine". Aix-Marseille 2, 1999. http://theses.univ-amu.fr.lama.univ-amu.fr/1999AIX20662.pdf.
Texto completo da fonteParent, Audrey. "Découverte de nouveaux complexes protéiques impliqués dans la synthèse et le transport intracellulaire des récepteurs couplés aux protéines G". Thèse, Université de Sherbrooke, 2010. http://savoirs.usherbrooke.ca/handle/11143/4304.
Texto completo da fonteDesfarges, Sébastien. "Transport intracellulaire et intégration du VIH-1 : implication de l'intégrase rétrovirale". Bordeaux 2, 2007. http://www.theses.fr/2007BOR21485.
Texto completo da fonteHIV-1 integrase (IN) is the key enzyme catalyzing the proviral DNA integration step. In this study, we have shown that HIV-1 IN expressed as the sole retroviral protein in budding yeast S. Cerevisiae was sufficient to catalyze the complete integration of a DNA containing two viral LTRs into the nuclear genome. IUsing this model, we demonstrated the RAD51 dependent pathway of homologous recombination (HR) down regulates the integration activities catalyzed by IN both in vitro and in yeast. Moreover, the molecular bases of the HIV-1 retrotranscription complex (RTC) intracellular trafficking are still poorly understood. We report in yeast that IN accumulates at the Microtubule Organization Center (MTOC) before being imported into the nucleus A kinetic of IN movement in cells revealed that IN and Stu2p, a microtubule associated protein, co-migrated towards the nuclear periphery followed its nuclear import. Microtubules depolymerisation by nocodazole or IN expression in a Dyn2p deficient strain (dynein light chain 2, homologue to human LC8) prevented accumulation of IN near the nuclear envelope, inhibited its transport into the nucleus thereby blocking integration activity. Then, we confirmed that the transport mechanism of IN in human T cells, an HIV-1 permissive cell line, and yeast are very similar. Further these findings suggest that IN may play a role in the intracellular translocation of the RTC. To verify the obtained results in the viral context, we infected CD4-expressing HeLa cells with fluorescently labelled HIV pseudo-viruses. We used HIV pseudo-viruses either with wt IN or with mutated IN. Comparing the transport of the RTC toward the nuclear periphery we showed that IN mediated this translocation
Chabrillat, Marion. "Etude du mouvement des mélanosomes sur les filaments d' actine : rôle des protéines Rab8 et myosine VI". Paris 6, 2005. http://www.theses.fr/2005PA066391.
Texto completo da fonteEcard, Jason. "Mécanismes de tri et voies de transport intracellulaire des protéines de la membrane du lysosome". Electronic Thesis or Diss., Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2019SORUS094.pdf.
Texto completo da fonteMore than sixty different proteins are inserted into the membrane of the lysosome, participating in the various functions of this organelle. But the intracellular trafficking pathways that lead lysosomal membrane proteins (LMPs) to this organelle are not well understood. Interestingly, some LMPs exhibit abnormal intracellular localisations in some cancers. This is the case of the glycoprotein LAMP1 which is overexpressed at the cell surface in several cancers, from where it plays several roles in tumour aggressiveness. Thanks to the Retention Using Selective Hooks (RUSH) system, allowing the synchronisation of the transport along the secretory pathway, we have shown that neosynthesized LAMP1 reaches the plasma membrane before entering endosomes. Comparing the routes followed by different LMPs also revealed that LAMP1 and LIMP2 are sorted at the Golgi apparatus, LIMP2 being concentrated in characteristic vesicular and clathrin-free structures. We have also shown that, surprisingly, this sorting at the level of the Golgi apparatus is independent of clathrin adapters recruitment signals carried in the C-terminal tails of these two LMPs. To investigate what mechanisms might be involved in the overexposure of LAMP1 at the cell surface of certain cancers, we also performed a gene knock-out screen based on CRISPR-Cas9 technology. We selected genes whose inactivation affected LAMP1 levels at the surface and obtained many candidate genes that are under study
Dauloudet, Olivier. "Étude théorique des phénomènes de transport intracellulaire hors-équilibre thermodynamique : rôle du couplage entre transport actif et diffusif en volume confiné". Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTS166/document.
Texto completo da fonteHow cells constantly remodel their intracellular space is one of the most astonishing self-organized phenomena in Nature. In order to do that, eukaryotic cells exploit the Brownian diffusion of macromolecules or organelles on small scales combined with active transport phenomena along cytoskeletal filament driven by motor proteins. Despite the important effort in the physico-mathematical community working on these biological issues, it is still very difficult to rationalize the motion of organelles (and in general of matter) inside the cell. In this thesis, we approach this problem by generalizing the theoretical analysis of a paradigmatic physico-mathematical model of non-equilibrium transport of motor proteins (called TASEP) to study the impact that a finite volume and a finite concentration of transporters have on their distribution in the cytosol and along the cytoskeleton. In particular, this requires inventing a new methodology in order to solve the problem where diffusive motion or transporters in the cytoplasm is coupled with directed collective transport along one or many cytoskeletal filaments. New interesting phenomena and regimes appear with respect to recent studies in literature. Moreover, the methodology developed so far, allow a fast and efficient investigation of complex systems behaviors for which numerical simulation can result very time consuming.The thesis is organized as follows. The first chapter is dedicated to an introduction on the topic and to the definition of biological and physical notions necessary for the research work presented. The second chapter tackles an approximate solution for the case of directed transport on a single cytoskeletal filament embedded in the cytosol, where the finite volume and the finite concentration of particles modify qualitatively and quantitatively the phase diagrams describing the average density and flux of transporters along the filament. We then discuss the physical conditions for which this approximated solution is no more valid. In order to overcome this difficulty, in chapter three we describe a novel method, inspired by the “images-method” to compute solutions of the Poisson equation in electrostatics, which allows for the first time (at our knowledge) to compute analytically the distribution of transporters in volume, i.e. the cytosol, without any approximated assumption. Importantly, the method can be easily generalized to any kind distribution or network of filaments and to other mechanisms of collective transport along the filaments. This makes possible to explore stationary regimes and new phenomena that can be hardly studied by stochastic simulations due to the complexity of the processes and the spatial extension of the system. Chapter four focuses on the innovative methodology of computation. Chapter five discusses miscellanea of problems and openings related to the topic studied. We end this thesis with general conclusions focusing on physical, biophysical and biological implications.The various results obtained have an impact on our general understanding on complex, collective and non-linear transport processes in situations and phenomena where transporters can move in spaces with different physical dimensions with interesting implications for biology, non-equilibrium statistical mechanics and the physico-mathematical theory of traffic and logistics
Gomord, Véronique. "Contrôle de l'adressage de la sporamine dans la cellule végétale". Rouen, 1994. http://www.theses.fr/1994ROUES054.
Texto completo da fontePoisson, Nicolas. "Les protéines issues du gène de la phosphoprotéine rabique : étude du trafic intracellulaire et identification de partenaires cellulaires". Paris 6, 2003. http://www.theses.fr/2003PA066261.
Texto completo da fonteSaint-Jean, Bruno. "Etude de la voie de transport assurée par le récepteur d’adressage vacuolaire BP80". Rouen, 2006. http://www.theses.fr/2006ROUES037.
Texto completo da fonteBP80 is a vacuolar receptor responsible for sorting proaleurain from the trans-Golgi network. The complex receptor-ligand is packed into shuttle vesicles that are directed and fused to a prevacuolar compartment where the lower pH induces the dissociation between the receptor and the proaleurain. This latter matured and released in the lytic vacuole. Beside the fact that BP80 uses clathrin coated vesicles for its traffic, we have no other indication on the signals in the cytoplasmic tail used by BP80 traffic. In an attempt to identify trafficking signals, we fused the GFP to the transmembrane and the cytosolic domains of BP80 and called the resulting fusion protein GFP-PS1. Like the native vacuolar receptor, GFP-PS1 accumulates and cycles in the same cell compartment. We then introduced single or two mutation(s) in the cytosolic portion of GFP-PS1. Using this approach, we identify two important sorting signals, which participates to recycling and endocytic events of BP80
Blot, Guillaume. "Caractérisation de deux nouveaux partenaires du domaine cytoplasmique de la glycoprotéine d'enveloppe du VIH-1 : tIP47 et Luman". Paris 7, 2003. http://www.theses.fr/2003PA077202.
Texto completo da fonteRenault, Noémie. "Trafic intracellulaire de la protéine Gag du virus Foamy". Paris 7, 2009. http://www.theses.fr/2009PA077154.
Texto completo da fonteFoamy viruses (FVs) are complex exogenous animal retroviruses that differ in many aspects of their life cycle from the orthoretroviruses such as human immunodefîciency virus (HIV). In particular, in FVvs, Gag and Pol proteins are expressed independently of one another, and both proteins undergo single clivage events. None of the conventional Gag landmarks of exogenous retroviruses, such as the major homology region or Cys-His motifs, are found in this protein. Instead, FV Gag harbors conserved C-terminal basic motifs, referred to as Gly-Arg (GR) boxes. Although the first GR (GRI) box binds viral nucleic acids and is required for viral genome packaging, the second (GRII) harbors a nuclear localization sequence (NLS) at its C-terminus, targeting Gag to the nucleus early after infection. GRII also contains a chromatin binding sequence (CBS) in its N-terminus, tethering the FV incoming pre-integration complex onto host chromosomes. The present work focuses on the structural Gag proteins, in early and late stages of infection. Troviral Gag proteins are involved in early stages of infection such as trafficking of incoming viruses nd nuclear import. FV Gag protein uses the microtubule network to reach the nucleus. In cycling cells,FV articles are structured at the centrosome 4 h post-infection. Then, the viral protease helps capsid for ncoating. In quiescent cells, we have shown that viral particles remain structured at the centrosome during everal weeks and that uncoating does not occur : this step is a limiting factor for infection although viral articles are still infectious. Upon cells reactivation, viral capsids undergo proteolysis and disassembly, llowing infection to proceed. During the late stages of infection, Gag undergoes transient nuclear trafficking after it synthesis, before returning back to the cytoplasm for capsid assembly and virus egress. The functional role of this nuclear stage, as well as the molecular mechanisms responsible for Gag nuclear export, are not understood. Here, we identify a leptomycin-sensitive nuclear export sequence (NES) within the N-terminus of the primate foamy virus Gag protein that is absolutely required for the completion of late stages of virus replication. Point mutation of conserved residues within this motif leads to nuclear retention of Gag and dramatically affects viral replication. Moreover, complementation experiments demonstrate that nuclear export-defective Gag mutants negatively interfere with virus release by sequestering wild-type Gag in the nucleus
Viranaicken, Wildriss. "Etude structurale et fonctionnelle des facteurs Ilf3 et NF90, deux protéines impliquées dans le routage intracellulaire des ARN messagers". Paris 6, 2005. http://www.theses.fr/2005PA066365.
Texto completo da fonteSiffroi-Fernandez, Sandrine. "Rôle des motifs N-glycanniques et des protéines chaperons sur la maturation et le transport intracellulaire du récepteur de la thyrotropine". Aix-Marseille 2, 2001. http://theses.univ-amu.fr.lama.univ-amu.fr/2001AIX20666.pdf.
Texto completo da fonteAkarsu, Hatice. "Etudes structurales et fonctionnelles des protéines virales impliquées dans le trafic intracellulaire du génome du virus de la grippe". Phd thesis, Université Joseph Fourier (Grenoble), 2005. http://tel.archives-ouvertes.fr/tel-00011131.
Texto completo da fontela cellule hôte par endocytose, libère dans le cytoplasme ses vRNPs qui gagnent ensuite le noyau cellulaire pour être transcrites et répliquées. Les vRNPs sont importées via l'hétérocomplexe des importines alpha/beta. La NP, composant majoritaire des vRNPs, pourrait être impliquée dans cette étape et serait aussi un candidat idéal dans la mise au point de drogues antivirales. Nous avons voulu déterminer les caractéristiques structurales de
NP en complexe avec l'importine alpha 5 humaine. Grâce à la technique de microscopie électronique à transmission, nous avons obtenu un premier
modèle à basse résolution du complexe NP/importine alpha.
Dans le noyau, les vRNPs sont étroitement liées à la chromatine. En phase tardive du cycle viral, la protéine matricielle M1 se lierait aussi à la chromatine, peut-être pour décrocher les vRNPs. Nous avons pu montrer, par la technique de sédimentation, que les vRNPs se lient aux queues des histones, alors que M1 se fixe sur le domaine globulaire des octamères d'histones.
En fin de cycle viral, les vRNPs amplifiées sortent du noyau. Nos tests enzymatiques, d'interaction sur billes et en sédimentation montrent que les protéines virales M1 et NEP servent d'adaptateurs entre les vRNPs et le système d'export nucléaire CRM1/RanGTP. Nous avons aussi obtenu la
structure cristallographique du domaine C-terminal de NEP se liant à M1.
Deroubaix, Aurélie. "Etude de la localisation intracellulaire de la protéine core du virus de l’hépatite B humaine et de ses multimères". Thesis, Bordeaux 2, 2011. http://www.theses.fr/2011BOR21907/document.
Texto completo da fonteHepatitis B is a liver inflammation caused by the Hepatitis B virus (HBV). It is responsible of one to two millions deaths per year in the world. HBV is the cause of important liver damages and may lead to cirrhosis and hepatocellular carcinoma.HBV is a member of hepadnaviral family. It has a capsid composed of 240 copies of the same protein: the core protein. In literature, patients’ biopsies showed that capsid is found either in the nucleus or in the cytoplasm or both compartments of hepatocytes. In general, a cytoplasmic localization is related to an advanced state of the disease.In our study, we observed that in HuH-7 cells, core protein alone has a nuclear localization, whereas in viral context it is essentially found in the cytoplasm. We verified that these observations were not due to culture conditions. Then, we demonstrated that the cytoplasmic localization of core was due to viral factors. The viral polymerase is implied by its TP domain. The second component is the viral pregenomic RNA, by its Epsilon stem loop structure. At last, core localization is also influenced by the phosphorylation state of its serines 157, 170 and 172.Thus, we demonstrated that the core protein traffic is very complex and regulated by different viral and cellular factors. This work will further study the regulation of intracellular trafficking of the core protein and allow a better outcome for the infected patients
Driouich, Azeddine. "Etude du rôle de la glycosylation dans l'exportation des protéines par des suspensions cellulaires de sycomore (acer pseudoplatanus l. )". Rouen, 1990. http://www.theses.fr/1990ROUE5018.
Texto completo da fonteDenmat-Ouisse, Lise-Anne. "Rôle de la N-glycosylation et du repliement lors du transport des protéines solubles dans la cellule végétale". Rouen, 1998. http://www.theses.fr/1998ROUES044.
Texto completo da fonteSamih, Nezha. "Expression et adressage du transporteur de glucose Glut-1 dans les cellules épithéliales thyroïdiennes". Aix-Marseille 2, 2001. http://theses.univ-amu.fr.lama.univ-amu.fr/2001AIX20656.pdf.
Texto completo da fonteRaio, vilela Fernando Augusto. "Structural characterization of JIP3 recruitment by Kinesin-1". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS123.
Texto completo da fonteThe intracellular transport of cargos is a crucial process on eukaryotic cells, and notably in neurons, in order to regulate different functions as cell’s maturation and synaptic transmission. The Kinesin-1 is a molecular motor capable of transporting different types of cargos as organelles, vesicles and macromolecular assemblies along the microtubules. It is a heterotetramer composed by a homodimer of heavy chains (KHC) bound to two light chains (KLC), where both KHC and KLC are capable of cargos recruitment. One of the first identified cargos of Kinesin-1 is JIP3/4 (JNK-Interacting Protein 3/4), which are also adaptor proteins, intermediating the transport of other cargos. Kinesin-1 recruits JIP3/4 by two different and independent modes, (i) via KHC and (ii) via KLC. Therefore, JIP3/4 recruitment by KHC and KLC activates the motility of Kinesin-1, by distinct mechanisms, allowing the intracellular transport of cargos and the associated functions in neurons. During my PhD, I contributed to the characterization of the dual binding mode of Kinesin-1 and JIP3/4 by bioinformatical, biochemical/biophysical and structural approaches. This work allowed a better understanding of the cargos’ recruitment by Kinesin-1, as well as the molecular mechanisms of Kinesin-1 activation by JIP3/4
Ben, Ahmed Awatef. "Implication de la O-GlcNAcylation dans le trafic intracellulaire : impact de la O-GlcNAc Transférase (OGT) sur le positionnement du système endolysosomal et cartographie de son interactome proximal par BioID". Electronic Thesis or Diss., Université de Lille (2022-....), 2024. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2024/2024ULILS101.pdf.
Texto completo da fonteO-GlcNAcylation is a reversible post-translational modification orchestrated by O-GlcNAc transferase (OGT), which transfers a single GlcNAc residue from UDP-GlcNAc to Ser/Thr residues of proteins, and O-GlcNAcase (OGA), which hydrolyses the O-glycosidic bond. O-GlcNAcylation regulates the biological properties of many target proteins, including their stability and enzymatic activity. O-GlcNAcylation is part of the cellular response to various stresses, allowing cells to adapt to their microenvironment. In particular, it has been shown that during nutritional stress, changes in the O-GlcNAc status of specific proteins regulate the autophagic flux, thereby ensuring cell survival. This catabolic process relies on the formation and maturation of autophagic vacuoles, which fuse with lysosomes to degrade cytoplasmic components and recycle them into metabolic precursors. However, there is limited data on the role of OGT in basal autophagy, which occurs under physiological conditions to degrade damaged proteins and organelles to maintain cellular homeostasis, particularly in the colon epithelium.In this context, the first aim of my thesis was to understand how OGT activity regulates basal autophagy in human colon cells, both cancerous and non-cancerous, cultured under nutrient-rich conditions. Using cellular approaches and confocal imaging, my results show that inhibition or depletion of OGT induces a blockade of the basal autophagic flux in both cell lines by altering autophagosome maturation. OGT inhibition is accompanied by an abnormal perinuclear accumulation of lysosomes and endosomes, which is associated with a defect in the colocalisation of a key regulatory protein of the endolysosomal system, the Rab7 GTPase. We then used the BioID strategy to identify the cytoplasmic proximal interactome of OGT, which is sensitive to its catalytic activity and glucose supply. BioID analysis shows that inhibition of OGT disrupts its proximal interaction with two proteins involved in the Rab GTPase activation cycle, RabGGTA and GDI1. We also identified the kinesin KIFC1 and two subunits of dynein, which are molecular motors involved in the intracellular transport of organelles along the microtubule network. Confocal imaging results suggest that OGT inhibition antagonistically alters the subcellular localisation of these motor proteins.My dissertation work reveals a critical role for OGT in basal autophagy and the positioning and homeostasis of the endolysosomal system in human cells. These findings open new perspectives for understanding the molecular mechanisms regulating these fundamental cellular processes
Gata, Gabriel. "Regulated export of G-protein coupled receptors". Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05T066.
Texto completo da fonteThe largest family of membrane receptors is constituted by conserved seven-membrane domain spanning receptors, the G-protein coupled receptors (GPCRs). They are involved in numerous cell responses and diseases thus being a major drug target. Receptor function is determined by the amount of active receptors at the cell surface, which depends on various parameters, such as the biosynthetic rate, the export to the cell surface from internal stores, the endocytosis and post-transcriptional modifications (i.e. phosphorylation). Only recently, the importance of the regulated export has emerged, shedding new light on the physiological role of receptor retention, release, chaperoning and escorting. This work concerns the regulated export mechanisms of two members of the GPCRs family, the chemokine receptor 5 (CCR5) and the metabotropic receptor of the g amino butyric acid (GABAB). Whereas CCR5 is likely a homo-dimer of 2 identical protomers, GABAB is an obligatory hetero-dimer of 2 distinct subunit known as GB1 and GB2. Both CCR5 and GB1 are retained in intracellular compartments (the ER and the Golgi) from which they are released in response to external signals (CCR5) and/or interaction with “private escort proteins” (CD4 for CCR5 and GB2 for GB1). The main goal of our work was to understand the mechanism of retention of these receptors and its regulation. In this context, we determined using biochemical and biophysical approaches that these GPCRs specifically interact with the members of the Prenylated Rab Acceptor Family (PRAF). These proteins are resident either in the ER (PRAF2 and PRAF3) or in the Golgi apparatus (PRAF1) where they function as receptor gatekeepers. Indeed, we could document for PRAF2 that this protein likely interacts directly with previously identified receptor retention motifs and inhibits receptor egress from the ER and subsequent trafficking to the plasma membrane. In the context of the GABAB receptor, PRAF2-dependent retention of GB1 can be overridden by GB2 via simple competition. Perturbing the stoichiometry of PRAF gatekeepers respective to that of receptors significantly perturbs receptor function both in vitro and in vivo. Because PRAFs are ubiquitous and seem to interact with many other GPCRs, they might represent major regulators of receptor function both in physiological and pathological conditions
Sidelarbi, Khadidja. "Implication du chaperome de la protéine F508del-CFTR dans son transport intracellulaire et/ou sa dégradation : rôle des lectines EDEMs et la mannosidase du RE". Thesis, Poitiers, 2017. http://www.theses.fr/2017POIT2286/document.
Texto completo da fonteNumerous genetic diseases are directly associated to the recognition of misfolded proteins by the endoplasmic reticulum (ER) quality control, leading to their retention and subsequently their retrotranslocation to the cytosol for degradation. In the case of mutated glycoproteins such as F508del-CFTR (Cystic Fibrosis Transmembrane conductance Regulator), causing CF pathology, mannose trimming is a key step of this process. Our objective was to identify and characterize molecules targeting ER-mannosidases activity, with the goal to restore F508del-CFTR to the plasma membrane.First, we tested multivalent derivatives, based mainly on Deoxymannojirimycin (DMJ), a specific inhibitor of α-mannosidasesI and revealed their better corrective effect on F508del-CFTR and their mechanism of action. Then we explored the mechanism explaining the higher efficiency of the multivalents compared to the monovalent. Finally, we focused on the role of key players of mannose trimming, ER-α1,2-mannosidase I (ERManI) and EDEMs (ER degradation-enhancing α-mannosidase-like protein) proteins on F508del-CFTR trafficking defect. We showed the implication of ERManI, EDEM1 and EDEM2 in F508del-CFTR retention, using a siRNA strategy. In conclusion, our study highlights these proteins as potential pharmacological targets to develop correctors for the F508del-CFTR trafficking defect
Catez, Frédéric. "Identification et caractérisation des signaux de transport intracellulaire de la protéine US11 de HSV-1 : définition des modalités de la localisation nucléaire et nucléolaire". Lyon 1, 2000. http://www.theses.fr/2000LYO10172.
Texto completo da fonteMarchal, Michelle. "La valence du ligand du récepteur à la transferrine 1 (TfR1) détermine son routage intracellulaire". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS418.
Texto completo da fonteThe transferrin receptor (TfR1) is a highly conserved receptor that allows the entry of iron (Fe) linked to transferrin (Fe-Tf) into cells. Once internalized, Fe separates from the Tf and is exported in the cytoplasm whereas the complex Tf/TfR1 is recycled to the cell membrane. TfR1 is internalized by a clathrin mediated endocytosis and can be either recycled to the cell membrane through the rapid pathway or be routed towards the endosomal recycling compartment (ERC). Once in the ERC, the TfR1 can be either recycled to the cell membrane through the slow pathway or be routed towards lysosomes. Many proteins regulates the routing of internalized proteins such as Rab proteins. They are small GTPases involved in molecular exchanges between the different cellular compartments.Being the main mode of entry of iron into cells, TfR1is expressed by almost every cells and is overexpressed by highly proliferative cells including some cancer cells. TfR1 is extensively studied as a therapeutic target for the development of new anti-cancer strategies. A24 is a murine anti-TfR1 whose anti-proliferative and pro-apoptotic roles were demonstrated in several hematological malignancies.We wondered how A24 binding on TfR1 can produce different effects from Fe-Tf binding. By the manufacturing of a Fab fragment, we first demonstrated that TfR1 fate depends on its ligand’s valency. We then demonstrated that the monovalent binding of TfR1 with Fe-Tf or the Fab leads to its recycling without going through the ERC. We also showed that the divalent binding of the TfR1 by A24 leads to its routing from the ERC to lysosomes through a Rab12 dependent pathway
Bouvet, Samuel. "Lipides et trafic : rôles de GBF1, facteur d’échange de la petite protéine G Arf1". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA112172/document.
Texto completo da fonteThe eukaryotic cell physically separates its functions within several membrane-bound organelles, which communicate using vesicles. Vesicular trafficking is under the control of small GTPases that exist as an inactive GDP-bound form and an active GTP-bound form. The switch between GDP and GTP is catalyzed by a guanine nucleotide exchange factor (GEF). On cis-Golgi membranes, Arf1, activated by the large GEF GBF1, recruits the COPI coat. COPI coated vesicles ensure the retrograde transport from the Golgi to the ER. Recently, GBF1 has been implicated in other pathways, such as the life cycle of various viruses and lipid droplet metabolism.Lipid droplets (LD), the major lipid storage organelle, play a major role in lipid homeostasis within the cell. LDs are connected to membrane trafficking and are therefore under the control of GTPases. In previous studies, our team showed that GBF1 localizes around LDs and that it is required for protein loading onto the LD surface. Here, data support the idea that GBF1 localizes to the LD surface. Using cell biology tools and microscopy, we identified, within GBF1, a lipid binding domain. In this domain, a single amphipathic helix is necessary and sufficient for LD targeting in cells. The regulation of GBF1 localization relies on interaction with Rab1 (data support a Rab1-Arf1 cascade between the ER and the Golgi) and on intramolecular interactions between GBF1 domains
Vincent, Patrick. "Trafic intracellulaire des phospholipides du système endomembranaire chez un végétal supérieur Allium porrum L. : étude de la relation synthèse-transport de la phosphatidylsérine à la surface cellulaire. Caractérisation chez ce végétal d'ADNc codant pour des protéines membres potentiels de la famille des SNAREs Ykt6p, impliquée dans le transport RE-Golgi". Bordeaux 2, 2000. http://www.theses.fr/2000BOR28816.
Texto completo da fonteThe work presented in this thesis concerns the study of the biogenesis of the plasma membrane in higher plants, on the model of Allium porrum. The plasma membrane of the eukaryotes is enriched in phosphatidylserine, where it plays a fundamental role in various biological activities, notably in the membrane traffic, allowing for exchanges in the extracellular environment. The studies carried out on the relationship between the synthesis and the transport of this phospholipid to the cellular surface, have demonstrated that there may be two different origins : vesicular, through the endoplasmic reticulum-Golgi apparatus pathway, and locally, by synthesis activity on the plasma membrane. Very long chain fatty acid species are sorted and directed in priority towards the secretion pathway. They are synthetized in the endoplasmic reticulum by a Base exchange activity, but also at the cellular surface with the same enzyme activity. In order to characterise vesicles which are rich in phosphatidylserine, formed and isolated from the endoplasmic reticulum in an cell-free system, studies have been carried out on the research of cDNA coding for proteins which are potentially members of Ykt6p SNAREs. In animals and yeast cells, this family is involved in the specific targeting of vesicles which come from the endoplasmic reticulum and which are to be used in the Golgi apparatus
Richer-Potier, Carole. "Identification de signaux impliqués dans la rétention d'une protéine membranaire de type I : la calnexine, dans le réticulum endoplasmique (RE) de la cellule végétale". Rouen, 2000. http://www.theses.fr/2000ROUES054.
Texto completo da fonteCastro, Cruz Monica del Carmen. "The impact of the syndecan-PDZ interactome on endosomal trafficking and extracellular vesicle composition". Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0302.
Texto completo da fonteSyndecans form a family of four transmembrane proteins that are substituted with heparan sulfate. By virtue of these extracellular carbohydrate chains, syndecans control the signaling of a plethora of growth factors and adhesion molecules. Another remarkable feature of syndecans is the conservation of their intracellular domain through evolution. This domain contains a C-terminal motif that can mediate interaction with PDZ proteins. PDZ interactions are promiscuous and PDZ proteins control various aspects of cell signaling and cell-cell communication. Four syndecan-PDZ interactions have been described so far and all these interactions have broad effects on cell behavior. In particular, it was documented that syndecan-syntenin interaction has impact on the intracellular trafficking of heparan sulfate cargo. Moreover syndecan-syntenin controls the biogenesis of exosomes, extracellular organelles emerging as important mediators of cell-cell communication in health and diseases. The human proteome contains 150 PDZ proteins and 266 PDZ domains. Here we started addressing the complexity of the syndecan-PDZ interactome and tested for its impact on membrane trafficking and on the composition of extracellular vesicles. Our work paves the way for a better understanding of the molecular mechanisms and networks controlling cell-cell communication in health and disease
Dalkara, Deniz. "Transfert intracellulaire de protéines". Université Louis Pasteur (Strasbourg) (1971-2008), 2006. http://www.theses.fr/2006STR13021.
Texto completo da fonteDuring this thesis we have developped an efficient method for intracytoplasmic protein delivery into mammalian cells. This method employs cationic lipids, previously used in gene delivery, to complex proteins and to transport them into the cytoplasm of cells in culture. In the last decade, the most commonly used approach for protein expression has been the transfection of its gene. Considering that the aim of transfection is to produce proteins and that synthetic vectors are capable of efficient gene delivery to mammalian cells ; we studied direct intracellular protein delivery using these carriers. The direct delivery of functionally active proteins can be helpful in overcoming some bottlenecks of transfection mediated protein production. We thus initiated studying intracellular protein delivery using the cationic lipid DOGS. We studied the interaction of the cationic lipid with bovine serum albumin and determined the different parameters involved in creating complexes that are well internalised by cells. We applied the notions acquired during the intracellular delivery of this model protein to a variety of other proteins with different physico-chemical properties in order to apprehend the contribution of these properties to the processus of complexation and vectorisation by DOGS. We successfully delivered a variety of proteins such as monoclonal antibodies, an enzyme, and a phycobilliprotein into different mammalian cell lines. Furthermore, we demonstrated that the antibodies delivered using this method retain their ability to bind their antigens once they reach the cytoplasm. From this point of view, intracellular protein delivery with cationic lipids can be considered another way to interfere with cellular activities. During this thesis, we have thus developped an original strategy for the intracellular delivery of proteins which will allow us to deliver, in vivo, a large variety of proteins for therapeutic purposes or functional studies
Sloves, Pierre-Julien. "La sortiline et les voies endosomales apparentées sont les éléments clefs pour la biogenèse des organites apicaux et la virulence chez Toxoplasma gondii". Thesis, Lille 2, 2012. http://www.theses.fr/2012LIL2S020/document.
Texto completo da fonteToxoplasma gondii, the causative agent of toxoplasmosis belongs to the phylum named Apicomplexa that also contains Plasmodium falciparum, the causative agent of malaria and others parasites such as Cryptosporidium or Eimeria. Apicomplexan parasites are uniquely characterized by specific organelles, rhoptries and micronemes, which are located at the apical end of the parasite. These organelles are involved in the control of host-pathogen interactions. The proteins in these secretory organelles are trafficked through the endolysosomal system. However, the receptors that play key roles in protein sorting and biogenesis of these apical organelles remain to be identified. Sortilin is a type I transmembrane receptor known in humans for protein sorting and trafficking. Here, we report that the homologue of sortilin in T. gondii designated TgSORTLR for “Toxoplasma gondii SORTilin Like Receptor” is localized to Golgi and post-Golgi compartments and transports proteins into rhoptries and micronemes via their specific interactions with its luminal domain. We demonstrate that the C-terminus of TgSORTLR is also important for its subcellular localization through binding to cytosolic components of vesicular trafficking proteins known to be involved in anterograde and retrograde transports. The depletion of TgSORTLR using conditional knock-out strategy causes a complete rmis-localization of proteins of both rhoptries and micronemes, leading to the loss of these apical organelles. These mutants display a strong attenuation of the parasite virulence in mice with the absence of acute toxoplasmosis symptoms. Complementation of the strain lacking TgSORTLR showed that N-terminal region between 39-202 amino acids indicated that the N-terminus, similarly to the C-terminus is essential for its correct localization. We conclude that the full-length TgSORTLR protein is required for its biological functions as intracellular sorting receptor in T. gondii
Elias, Emmanuel. "Dynamique intracellulaire des protéines nucléolaires". Reims, 2005. http://www.theses.fr/2005REIMM203.
Texto completo da fonteThe nucleolus is the site where synthesis and maturation of ribosomal RNAs occur. The tandemly repeated rDNA genes are transcribed by RNA polymerase I associated to several transcription factors. Among them, the Upstream Binding Factor (UBF) is expressed from a unique gene by alternative splicing as two isoforms, UBF1 and UBF2. In order to visualize both variants, which are not discriminated by specific anti-UBF antibodies, we previously developed chimeric proteins between UBF1/UBF2 and GFP. Moreover, it is well-known that inhibition of RNA polymerase I by actinomycin D (AMD) (50 ng/ ml) induces a complex segregation of the nucleolar components as observed on cells fixed. In the present work, we addressed the 3D localisation of nucleolar proteins UBF1, UBF2, PAF53, Topoisomerase I, Fibrillarin, Nucleolin and B23 by confocal microscopy within fixed control KB cells and during the action of AMD. Furthermore, we followed the localisation of UBF1, UBF2 and Fibrillarin within living KB cells during the action of AMD. In order to study the complex 3D trajectories of the components containing GFP-UBF and GFP-fibrillarin during the nucleolar segregation, we used both classical visualization tools using (2D + time) modes and developed tools based on (3D + time) visualization procedure. Under action of AMD, the spots labelled by UBF aggregate and form caps localised at the nucleolar periphery. For fibrillarin, the rings observed in control cells evolved into spots under the treatment. Finally, these spots merged to form caps also localized at the nucleolar periphery. This study revealed a different kind of reorganization for both variants of UBF and Fibrillarin upon treatment
Cavelier, Adeline. "Complementarité des protéines de detoxication et trafic intracellulaire". Phd thesis, Université René Descartes - Paris V, 2007. http://tel.archives-ouvertes.fr/tel-00553511.
Texto completo da fonteCharlier, Caroline. "Analyse du transport intracellulaire du bornavirus". Toulouse 3, 2013. http://thesesups.ups-tlse.fr/2208/.
Texto completo da fonteBorna disease virus (BDV) is a neurotropic virus that establishes long-term persistence in the central nervous system. The cellular cycle of BDV remains poorly understood, in particular concerning the modalities of intracellular transport of viral ribonucleoparticles (RNP). During my Ph. D. , I developed several approaches aiming at a better understanding of the modalities of BDV transport. To track RNP transport in live, infected cells, we constructed a recombinant virus that can be fluorescently labeled. We analyzed viral dynamics in persistently and newly infected cells using live imaging. We also studied the molecular mechanisms of BDV transport in primary cultures of neurons and we demonstrated that RNP are transported by axonal endosomes
Nizak, Clément. "Développement d'outils pour l'étude de la dynamique de l'appareil de Golgi en interphase et en mitose". Phd thesis, Université Paris-Diderot - Paris VII, 2003. http://tel.archives-ouvertes.fr/tel-00190898.
Texto completo da fonteTout d'abord, j'ai utilisé la technique d'Interférence ARN, qui permet d'inhiber l'expression d'une protéine d'intérêt, et ainsi révélé la complexité de la régulation du transport golgien par la GTPase Rab6.
Ensuite, j'ai suivi une stratégie reposant sur l'imagerie in vivo du désassemblage et du réassemblage de l'appareil de Golgi au cours de la mitose, et ainsi mis en évidence une étape particulière du désassemblage golgien.
Enfin, le cœur de ma thèse a consisté en la production d'anticorps recombinants dirigés contre des protéines golgiennes par Phage Display, et le développement de leur utilisation pour tracer le comportement des protéines-cibles in vivo.
Molla, Herman Anahi. "Trafic intracellulaire et ciliogénèse". Paris 5, 2009. http://www.theses.fr/2009PA05T020.
Texto completo da fonteThe primary cilium (PC) is present in almost all vertebrate cells and defects in its assembly/function are associated with a huge number of ciliopathies. PC seems to function as a mecanosensory antenna since is enriched in receptors, like the G-protein coupled receptors (RCPGs). Beta-arrestines (βarrs) 1 and 2 regulate GPCR at the cell membrane, suggesting that they could also play a role in cilia-associated GPCRs. We found that βarr2 is specifically localised to PC and that it interacts with Kif3A and 14-3-3, two proteins involved in ciliogenesis, suggesting a possible function of βarr2 in ciliogenesis. Indeed, βarr2 absence impedes PC formation. Nevertheless, this seems to be an indirect effect due to the fact that the absence of βarr2 leads to a cell over proliferation, preventing cilia formation. We also observed that PC is invaginated in what we call the ciliary pocket, which can be transitory or permanent, depending on the cell type, from which clathrin coated pits bud forming clathrine coated vesicles. This led us to study the role of clathrin adaptor complexes (AP) in ciliogenesis, and we could observe that API would be important for the morphology/orientation of PC. Thus, it is possible to imagine that the ciliary pocket serves as a membrane platteform for the docking of Golgi-coming vesicles or for endocytic process which could control ciliary components
Dürrbach, Antoine. "Role des myosines 1 dans le transport intracellulaire". Paris 6, 1997. http://www.theses.fr/1997PA066070.
Texto completo da fonteCosson, Pierre. "Mécanismes de formation de vésicules de transport intracellulaire". Aix-Marseille 2, 1989. http://www.theses.fr/1989AIX22070.
Texto completo da fonteMamane, Alexandre. "Transport intracellulaire par des moteurs moléculaires : étude théorique". Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066728/document.
Texto completo da fonteWe study two intracellular transport phenomena. They are powered by molecular motors. Motors general mechanisms are understood, but their interactions leads to emerging properties, and some of them have specialised functions.In the first part, we study the extraction of membrane tubes by myosin 1b supported by actin bundles. Myosin 1b is a non processive motor with catch bond property. It is implied in membrane trafficking at the Golgi apparatus level. We model this phenomenon in the frame of a collaboration with experimentalists. We show that catch bond effect induces a regime where tube extraction requires a giant length fluctuation, and the minimal number of motors allowing extraction is decreased. Tubes extracted by non processive motors do not show oscillatory regime. During tube growth motors can deplete with non processive motors. Our predictions are in good agreement with experimental observations.In the second part we study in collaboration with experimentalists the cytoplasmic streaming in C.elegans. Its function is supposed to be the mixing the cytoplasm. Its orientation reverses stochastically. Its movement is supported by microtubules and kinesins, that drive the endoplasmic reticulum at the cortical level. We model this phenomenon and show that the transition toward streaming is a spontaneous spatial symetry breaking. Our predictions are in good agreement with the experimental observations. The parameters values of the system optimize flow fluctuations, this could be the mechanism driving the mixing. Our predictions are in good agreement with experimental observations
Baratti-Elbaz, Catherine. "Internalisation et recyclage du récepteur de la TSH". Paris 11, 2000. http://www.theses.fr/2000PA11T058.
Texto completo da fonteThe TSH receptor is a G protein coupled receptor, with specific characteristics from the two high homologous lutropin (LH) and folliculostimulin (FSH) receptors (i) its large extracellular domain which is cleaved in two subunits (ii) its constitutive activity towards the cAMP transduction pathway and (iii) the existence of stimulating anti-receptor autoantibody implicated in hyperthyroïdism. Seant information is available on the intracellular trafficking of this receptor. Stahly transfected L cells expressing TSH receptor and anti-receptor antibodies were used to study by confocal and electron microscopies its cellular distribution and endocytosis. The TSH receptor was initially localized on the plasmalemma proper and in clathrin-coated pits. Lt was internalized through clathrin-coated vesicles. Constitutive endocytosis represented 10% of cell surface receptor molecules. Endocytosis was increased only 3 fold by the hormone. The majority of internalized receptor recycled to cell surface via smooth vesicles whereas hormone was degraded in lysosomes. This recycling was inhibited by administration of monensin and occurred via a caveolin-1 independent pathway. Microscopic studies repeated in primary cultures of human thyroid cells showed a baso-lateral distribution and a very similar endocytosis pathway. The LH receptor is endocytosed in high proportion and degraded in lysosomes. Colocalization studies with transferrin receptor confirmed that highly homologous LH and TSH receptors exhibit, when expressed in the same cells, very different cellular trafficking properties. The use of LHITSH receptor chimeras showed that transmembrane and intracellular domains contain information orienting the protein toward recycling or degradative pathways. The extracellular domain seems to play a role in the extent of internalization. These observations should now allow the determination of the molecular signals involved in these processes
Kuster, Aurélia. "SNARE et trafic membranaire intracellulaire : rôle de SNAP-47 nouveau partenaire des SNARE vésiculaires". Paris 7, 2013. http://www.theses.fr/2013PA077165.
Texto completo da fonteVesicular trafficking allows for protein and lipid transport between intracellular compartments. V-SNAREs, present at the vesicular membrane, and t-SNAREs, present at the target membrane, interact via their SNARE domains, and form a complex that allows membrane fusion. TI-VAMPNAMP7 is a v-SNARE localized in the Golgi apparatus, late endosomes and lysosomes, which plays a role in apical transport, neurite growth and cell migration. First, we showed that TI-VAMP is phosphorylated by c-src and that a phosphomimetic mutant activates its exocytosis. Secondly, by a proteomics approach, we found that TI-VAMP interacts with the t-SNARE SNAP-47. We highlighted that SNAP-47 interacts also with VAMP4 and VAMP8, and has a perinuclear localization, closed to the endoplasmic reticulum and the ERGIC. A carboxy-terminal domain deleted mutant still interacts with VAMPs 4, 7 and 8 and affects VAMPs 4 and 7 distribution, suggesting a role of SNAP-47 in the v-SNAREs' subcellular localization. Moreover, SNAP-47 mutant is partially delocalized to the nucleus. SNAP-47 possesses nuclear localization and export signais, and cell treatment with leptomycine B induces relocalization of the WT protein in the nucleus, suggesting a transit between nucleus and cytoplasm. Thus, SNAP-47 appears different from classical t-SNAREs and could potentially have a fonction in other mechanisms than membrane fusion. We suggest that SNAP-47 could play a role of chaperone by regulating its v-SNARE partners'localization
Bastin, Guillaume. "Les résidus cystéines en positions 2 et 12 de RGS4 influencent son trafic intracellulaire et ses fonctions". Thesis, Lille 1, 2013. http://www.theses.fr/2013LIL10003/document.
Texto completo da fonteRGS proteins (Regulator of G-protein Signaling) are potent inhibitors of heterotrimeric G-protein signaling. RGS4 attenuates G-protein activity in several tissues such that loss of its function may lead to bradycardia, diabetic cardiomyopathy, breast cancer cell invasion, insulin resistance and glucose intolerance. RGS4 has been localized to both plasma membrane and intracellular pools, however, the nature of its intracellular trafficking remains to be elucidated. G-protein inhibition requires the presence of RGS4 at the plasma membrane. In this work, we characterized the complementary roles of two putative palmitoylation sites on RGS4 to target intracellular compartments and plasma membrane. We identified palmitoylation on Cys2 and 12 respectively important for RGS4 endosomal targeting and plasma membrane localization, when mutations were introduced to the palmitoylation sites, RGS4 capability of inhibiting Gq-mediated signaling was impaired. As a continuum we identified two palmitoylating enzymes, DHHC3 and 7 as modulator of RGS4 localization and function. Knock downs of DHHC3 and 7 impaired RGS4 endosomal and plasma membrane targeting and capability of inhibiting M1-muscarinic receptor signaling. Finally we used live cell confocal microscopy to define RGS4 intracellular trafficking routes. Specifically Rab5 mediated RGS4 trafficking from the plasma membrane to intracellular compartments while Rab11 mediated RGS4 trafficking to the plasma membrane. Activation and inhibition of Rab5 and 11 routes impaired RGS4 capability of inhibiting M1-muscarinic receptor signaling pathway. These novel findings provide a strong rationale for future studies aimed at developing new strategies to increase the function of RGS4
Bensmail, Laila. "Contribution à l'étude de la régulation et de la sécrétion chez Myxococcus xanthus : utilisation comme sonde d'un gène codant une endoglucanase". Rouen, 1996. http://www.theses.fr/1996ROUES065.
Texto completo da fonteGirardin, Stephen. "Régulation de la voie de signalisation intracellulaire JNK/SAPK". Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13179.
Texto completo da fonteKlein, Sarah. "Application des outils de la physique statistique au transport intracellulaire". Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS090/document.
Texto completo da fonteMost processes in our daily life are far from equilibrium. The prime example is a cell and the transport occurring within. In this thesis intracellular transport is modeled by means of stochastic processes. For this, two different approaches are applied: the explicit mod- eling of active particles with internal degrees of freedom with characteristics as they were determined experimentally. And secondly, the collective effects occurring in many particle systems are studied in a phenomenological way by means of exclusion processes.In the explicit model one important result is given by the fact that force fluctuations are essential to capture the relevant motion characteristics. Further, the influence of the cellular environment creates counter-intuitive effects, like a possible inversion of the bias. The motion characteristics can be represented in a coarse-grained manner as an exclusion process for particles with internal states. Due to the resulting disorder in the hopping rates a density-dependent condensation occurs.In a second part, a two-lane exclusion model is studied. Two species in a tubular geometry inspired by filamentous fungi are considered.This can be seen as a minimal model exhibiting a phase transition from a low density phase to an intriguing phase with periodically changing particle densities
Boeuf, Julien. "Caractérisation des GASP, une nouvelle famille de protéines impliquées dans le trafic intracellulaire des récepteurs couplés aux protéines G". Université Louis Pasteur (Strasbourg) (1971-2008), 2008. https://publication-theses.unistra.fr/public/theses_doctorat/2008/BOEUF_Julien_2008.pdf.
Texto completo da fonteG protein-coupled receptors (GPCRs), one of the most important family of proteins, are distributed at the plasma membrane and are implicated in cell communication. They represent major targets for pharmaceutical drugs and their function is tightly regulated. Recently, we identified a novel family of proteins interacting with GPCRs. This family, called GASP, could have an important function in the proteolysis of the GPCRs, which is considered as a key feature of the regulation of GPCR activity. My PhD work focused on the domains of GASPs and GPCRs that are critical for the interaction between these two kinds of proteins, identifying a novel protein-protein interaction motif and designing and developing a small peptide capable of preventing this interaction. I also focused on the interaction between GASP-1 and -2 and the acetylcholine muscarinic M1 receptor, and the consequences of this interaction on the proteolysis of this receptor, showing for the first time the implication of GASPs in the intracellular trafficking of fast recycling GPCR. Finally, I studied the physiological role of GASP-1 using transgenic animals deficient in this protein. These mice showed notably alteration in behavioral and biochemical adaptive mechanisms related to acute and prolonged administration of cocaine. The regulation of the circadian rhythms was also assessed. Despite the lack of difference in terms of sleep-activity rhythm between wild-type and mutant mice, an interaction between the GASPs and the PER clock proteins, that leads to the modification of their subcellular distribution, was observed
Cailler, Françoise. "Étude du trafic intracellulaire de protéines membranaires de la famille de la néprilysine". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ47601.pdf.
Texto completo da fonteVannier, Christian. "Induction et activation intracellulaire de la lipoprotéine lipase de cellules adipeuses en culture". Nice, 1985. http://www.theses.fr/1985NICE4049.
Texto completo da fonteRavel, Sophie. "Mécanisme d'action des immunotoxines : étude de l'intériorisation et du transport intracellulaire". Montpellier 2, 1990. http://www.theses.fr/1990MON20186.
Texto completo da fonteLEPAGE-LEZIN, AGNES. "Maturation post-traductionnelle de la prosomatostatine, relation avec son transport intracellulaire". Paris 6, 1991. http://www.theses.fr/1991PA066204.
Texto completo da fontePollard, Hélène. "Metabolisme intracellulaire des plasmides therapeutiques (doctorat : biologie)". Nantes, 1999. http://www.theses.fr/1999NANT07VS.
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