Journal articles on the topic 'Spatial organiser of signalling'

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1

Kilpatrick, Laura E., and Stephen J. Hill. "The use of fluorescence correlation spectroscopy to characterise the molecular mobility of G protein-coupled receptors in membrane microdomains: an update." Biochemical Society Transactions 49, no. 4 (August 26, 2021): 1547–54. http://dx.doi.org/10.1042/bst20201001.

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It has become increasingly apparent that some G protein-coupled receptors (GPCRs) are not homogeneously expressed within the plasma membrane but may instead be organised within distinct signalling microdomains. These microdomains localise GPCRs in close proximity with other membrane proteins and intracellular signalling partners and could have profound implications for the spatial and temporal control of downstream signalling. In order to probe the molecular mechanisms that govern GPCR pharmacology within these domains, fluorescence techniques with effective single receptor sensitivity are required. Of these, fluorescence correlation spectroscopy (FCS) is a technique that meets this sensitivity threshold. This short review will provide an update of the recent uses of FCS based techniques in conjunction with GPCR subtype selective fluorescent ligands to characterise dynamic ligand–receptor interactions in whole cells and using purified GPCRs.
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2

Robertson, Elizabeth J., Dominic P. Norris, Jane Brennan, and Elizabeth K. Bikoff. "Control of early anterior-posterior patterning in the mouse embryo by TGF-β signalling." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 358, no. 1436 (August 29, 2003): 1351–58. http://dx.doi.org/10.1098/rstb.2003.1332.

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Prior to gastrulation the mouse embryo exists as a symmetrical cylinder consisting of three tissue layers. Positioning of the future anterior–posterior axis of the embryo occurs through coordinated cell movements that rotate a pre–existing proximal–distal (P–D) axis. Overt axis formation becomes evident when a discrete population of proximal epiblast cells become induced to form mesoderm, initiating primitive streak formation and marking the posterior side of the embryo. Over the next 12–24 h the primitive streak gradually elongates along the posterior side of the epiblast to reach the distal tip. The most anterior streak cells comprise the ‘organizer’ region and include the precursors of the so–called ‘axial mesendoderm’, namely the anterior definitive endoderm and prechordal plate mesoderm, as well as those cells that give rise to the morphologically patent node. Signalling pathways controlled by the transforming growth factor–β ligand nodal are involved in orchestrating the process of axis formation. Embryos lacking nodal activity arrest development before gastrulation, reflecting an essential role for nodal in establishing P–D polarity by generating and maintaining the molecular pattern within the epiblast, extraembryonic ectoderm and the visceral endoderm. Using a genetic strategy to manipulate temporal and spatial domains of nodal expression reveals that the nodal pathway is also instrumental in controlling both the morphogenetic movements required for orientation of the final axis and for specification of the axial mesendoderm progenitors.
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3

Galli-Resta, L. "Local, possibly contact-mediated signalling restricted to homotypic neurons controls the regular spacing of cells within the cholinergic arrays in the developing rodent retina." Development 127, no. 7 (April 1, 2000): 1509–16. http://dx.doi.org/10.1242/dev.127.7.1509.

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In the vertebrate retina neurons of the same type commonly form non-random arrays, assembled by unknown positional mechanisms during development. Computational models in which no two cells are closer than a minimal distance, simulate many retinal arrays. These findings have important biological implications, since they suggest that cells are determined as neurons of specific types before entering their arrays, and that local, possibly contact-mediated interactions acting exclusively among the elements of an array account for its assembly. This is here verified by combining experimental manipulations in normal and transgenic models with computational analysis for the cholinergic mosaics, the only arrays so far for which the development of spatial ordering is known quantitatively. When generalised, these findings suggest a plan for vertebrate retinal patterning, where homotypic interactions organise retinal arrays first, then local interactions between synaptic partners suffice to establish the topographical connections that support retinal processing.
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4

Yasuo, Hitoyoshi, and Patrick Lemaire. "Role of Goosecoid, Xnot and Wnt antagonists in the maintenance of the notochord genetic programme in Xenopus gastrulae." Development 128, no. 19 (October 1, 2001): 3783–93. http://dx.doi.org/10.1242/dev.128.19.3783.

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The Xenopus trunk organiser recruits neighbouring tissues into secondary trunk axial and paraxial structures and itself differentiates into notochord. The inductive properties of the trunk organiser are thought to be mediated by the secretion of bone morphogenetic protein (BMP) antagonists. Ectopic repression of BMP signals on the ventral side is sufficient to mimic the inductive properties of the trunk organiser. Resultant secondary trunks contain somite and neural tube, but no notochord. We show that inhibition of BMP signalling is sufficient for the initiation of the trunk organiser genetic programme at the onset of gastrulation. During late gastrulation, however, this programme is lost, due to an invasion of secreted Wnts from neighbouring tissues. Maintenance of this programme requires co-repression of BMP and Wnt signalling within the presumptive notochord region. To shed light on the molecular cascade that leads to the repression of the Wnt pathway, we looked for individual organiser genes whose overexpression could complement the inhibition of BMP signalling to promote notochord formation in the secondary trunks. Two genes, gsc and Xnot, were thus identified and shown to act in different ways. Xnot acts as a transcriptional repressor within the mesodermal region. Gsc acts in deeper vegetal cells, where it regulates Frzb expression to maintain Xnot expression in the neighbouring notochord territory. These results suggest that, during gastrulation, the necessary repression of Wnt/β-catenin signalling in notochord precursors is achieved by the action of secreted inhibitors, such as Frzb, emitted by gsc-expressing dorsal vegetal cells.
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5

Crozatier, Michèle, Bruno Glise, and Alain Vincent. "Connecting Hh, Dpp and EGF signalling in patterning of theDrosophilawing; the pivotal role ofcollier/knotin the AP organiser." Development 129, no. 18 (September 15, 2002): 4261–69. http://dx.doi.org/10.1242/dev.129.18.4261.

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Hedgehog (Hh) signalling from posterior (P) to anterior (A) cells is the primary determinant of AP polarity in the limb field in insects and vertebrates. Hh acts in part by inducing expression of Decapentaplegic (Dpp), but how Hh and Dpp together pattern the central region of the Drosophila wing remains largely unknown. We have re-examined the role played by Collier (Col), a dose-dependent Hh target activated in cells along the AP boundary, the AP organiser in the imaginal wing disc. We found that col mutant wings are smaller than wild type and lack L4 vein, in addition to missing the L3-L4 intervein and mis-positioning of the anterior L3 vein. We link these phenotypes to col requirement for the local upregulation of both emc and N, two genes involved in the control of cell proliferation, the EGFR ligand Vein and the intervein determination gene blistered. We further show that attenuation of Dpp signalling in the AP organiser is also col dependent and, in conjunction with Vein upregulation, required for formation of L4 vein. A model recapitulating the molecular interplay between the Hh, Dpp and EGF signalling pathways in the wing AP organiser is presented.
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6

Tossell, K., C. Kiecker, A. Wizenmann, E. Lang, and C. Irving. "Notch signalling stabilises boundary formation at the midbrain-hindbrain organiser." Development 138, no. 17 (July 27, 2011): 3745–57. http://dx.doi.org/10.1242/dev.070318.

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7

Carl, M., and J. Wittbrodt. "Graded interference with FGF signalling reveals its dorsoventral asymmetry at the mid-hindbrain boundary." Development 126, no. 24 (December 15, 1999): 5659–67. http://dx.doi.org/10.1242/dev.126.24.5659.

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Signalling by fibroblast growth factors (FGFs) at the mid-hindbrain boundary (MHB) is of central importance for anteroposterior neural patterning from the isthmic organiser. Graded suppression of FGF signalling by increasing amounts of a dominant negative FGF receptor provides evidence that in addition to anteroposterior patterning, FGF signalling is also involved in patterning along the dorsoventral axis at the MHB. FGF signalling at the MHB is required for the activation of the HH target gene spalt at the MHB. Our results indicate that FGF signalling mediates the competence of the MHB to activate spalt in response to SHH. This interdependence of the two signalling pathways is also found in the outbudding optic vesicle where HH requires functional FGF signalling to activate spalt in the proximal eye region.
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8

Sykes, T. G., A. R. Rodaway, M. E. Walmsley, and R. K. Patient. "Suppression of GATA factor activity causes axis duplication in Xenopus." Development 125, no. 23 (December 1, 1998): 4595–605. http://dx.doi.org/10.1242/dev.125.23.4595.

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In Xenopus, the dorsoventral axis is patterned by the interplay between active signalling in ventral territories, and secreted antagonists from Spemann's organiser. Two signals are important in ventral cells, bone morphogenetic protein-4 (BMP-4) and Wnt-8. BMP-4 plays a conserved role in patterning the vertebrate dorsoventral axis, whilst the precise role of Wnt-8 and its relationship with BMP-4, are still unclear. Here we have investigated the role played by the GATA family of transcription factors, which are expressed in ventral mesendoderm during gastrulation and are required for the differentiation of blood and endodermal tissues. Injection ventrally of a dominant-interfering GATA factor (called G2en) induced the formation of secondary axes that phenocopy those induced by the dominant-negative BMP receptor. However, unlike inhibiting BMP signalling, inhibiting GATA activity in the ectoderm does not lead to neuralisation. In addition, analysis of gene expression in G2en injected embryos reveals that at least one known target gene for BMP-4, the homeobox gene Vent-2, is unaffected. In contrast, the expression of Wnt-8 and the homeobox gene Vent-1 is suppressed by G2en, whilst the organiser-secreted BMP antagonist chordin becomes ectopically expressed. These data therefore suggest that GATA activity is essential for ventral cell fate and that subsets of ventralising and dorsalising genes require GATA activity for their expression and suppression, respectively. Finally, using G2en, we show that suppression of Wnt-8 expression, in conjunction with blocked BMP signalling, does not lead to head formation, suggesting that the head-suppressing Wnt signal may not be Wnt-8.
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9

Carnac, G., L. Kodjabachian, J. B. Gurdon, and P. Lemaire. "The homeobox gene Siamois is a target of the Wnt dorsalisation pathway and triggers organiser activity in the absence of mesoderm." Development 122, no. 10 (October 1, 1996): 3055–65. http://dx.doi.org/10.1242/dev.122.10.3055.

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Siamois, a Xenopus zygotic homeobox gene with strong dorsalising activity, is expressed in the dorsal-vegetal organiser known as the Nieuwkoop centre. We show that, in contrast to Spemann organiser genes such as goosecoid, chordin and noggin, Siamois gene expression is not induced following overexpression of mesoderm inducers in ectodermal (animal cap) cells. However, Siamois is induced by overexpressing a dorsalising Wnt molecule. Furthermore, like Wnt, Siamois can dorsalise ventral mesoderm and cooperate with Xbrachyury to generate dorsal mesoderm. These results suggest that Siamois is a mediator of the Wnt-signalling pathway and that the synergy between the Wnt and mesoderm induction pathways occurs downstream of the early target genes of these two pathways. Overexpression of Siamois in animal cap cells reveals that this gene can act in a non vegetal or mesodermal context. We show the following. (1) Animal cap cells overexpressing Siamois secrete a factor able to dorsalise ventral gastrula mesoderm in tissue combination experiments. (2) The Spemann organiser-specific genes goosecoid, Xnr-3 and chordin, but not Xlim.1, are activated in these caps while the ventralising gene Bmp-4 is repressed. However, the dorsalising activity of Siamois-expressing animal caps is significantly different from that of noggin- or chordin-expressing animal caps, suggesting the existence of other dorsalising signals in the embryo. (3) Ectodermal cells overexpressing Siamois secrete a neuralising signal and can differentiate into cement gland and, to a lesser extent, into neural tissue. Hence, in the absence of mesoderm induction, overexpression of Siamois is sufficient to confer organiser properties on embryonic cells.
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10

Monterisi, Stefania, and Manuela Zaccolo. "Components of the mitochondrial cAMP signalosome." Biochemical Society Transactions 45, no. 1 (February 8, 2017): 269–74. http://dx.doi.org/10.1042/bst20160394.

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3′-5′-Cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signalling is activated by different extracellular stimuli and mediates many diverse processes within the same cell. It is now well established that in order to translate into the appropriate cellular function multiple extracellular inputs, which may act simultaneously on the same cell, the cAMP/PKA signalling pathway is compartmentalised. Multimolecular complexes are organised at specific subcellular sites to generate spatially confined signalosomes, which include effectors, modulators and targets of the pathway. In recent years, it has become evident that mitochondria represent sites of compartmentalised cAMP signalling. However, the exact location and the molecular composition of distinct mitochondria signalosomes and their function remain largely unknown. In this review, we focus on individual components of the cAMP/PKA signalling pathway at distinct mitochondria subdomains represented by the outer and inner mitochondrial membranes, the intermembrane space and the matrix, highlighting some of the questions that remain unanswered.
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11

Murad, Khairiyah, Sharaniza Ab Rahim, and Hassanain Al-Talib. "Antimicrobial Effects of Tetraspanins: A New Turnabout in Treatment of Microorganisms." Malaysian Journal of Medical Sciences 29, no. 4 (August 29, 2022): 6–13. http://dx.doi.org/10.21315/mjms2022.29.4.2.

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Tetraspanins, a transmembrane protein is a ‘molecular organiser’ with diverse functions that promote a network of signalling involved in the cellular and pathological processes. Tetraspanins-enriched microdomains (TEMs) are the crucial feature for the protein-protein interactions in the cell membrane and are vulnerable to pathogens exploitation. Targetting the tetraspanins has shown to be effective against microbial infections although more research is needed to be performed. This article will review previous evidence that has successfully demonstrated the potential mechanism to target tetraspanins as an antimicrobial agent.
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12

Carballada, R., H. Yasuo, and P. Lemaire. "Phosphatidylinositol-3 kinase acts in parallel to the ERK MAP kinase in the FGF pathway during Xenopus mesoderm induction." Development 128, no. 1 (January 1, 2001): 35–44. http://dx.doi.org/10.1242/dev.128.1.35.

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Phosphoinositide 3-kinases (PI3Ks) are lipid kinases that can phosphorylate phosphaditylinositides leading to the cell type-specific regulation of intracellular protein kinases. PI3Ks are involved in a wide variety of cellular events including mitogenic signalling, regulation of growth and survival, vesicular trafficking, and control of the cytoskeleton. Some of these enzymes also act downstream of receptor tyrosine kinases or G-protein-coupled receptors. Using two strategies to inhibit PI3K signalling in embryos, we have analysed the role of PI3Ks during early Xenopus development. We find that a class 1A PI3K catalytic activity is required for the definition of trunk mesoderm during the blastula stages, but is less important for endoderm and prechordal plate mesoderm induction or for organiser formation. It is required in the FGF signalling pathway downstream of Ras and in parallel to the extracellular signal-regulated kinase (ERK) MAP kinases. In addition, our results show that ERKs and PI3Ks can synergise to convert ectoderm into mesoderm. These data provide the first evidence that class 1 PI3Ks are required for a specific set of patterning events in vertebrate embryos. Furthermore, they bring new insight into the FGF signalling cascade in Xenopus.
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13

Cheek, TR. "Spatial aspects of calcium signalling." Journal of Cell Science 93, no. 2 (June 1, 1989): 211–16. http://dx.doi.org/10.1242/jcs.93.2.211.

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14

Prior, Ian A. "Spatial diversity: Ras trafficking and signalling." Biochemist 25, no. 3 (June 1, 2003): 22–24. http://dx.doi.org/10.1042/bio02503022.

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Ras proteins are small monomeric G-proteins that play a central role in linking extracellular stimuli with the internal kinase cascades that are primarily involved in modulating cell proliferation and differentiation. Constitutively activated mutants of these proteins are found in many human cancers. Differences in the trafficking and plasma membrane localization of Ras isoforms play critical roles in regulating their function. New research is trying to understand the mechanisms behind, and consequences of, these differences.
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15

Bethani, Ioanna, Sigrid S. Skånland, Ivan Dikic, and Amparo Acker-Palmer. "Spatial organization of transmembrane receptor signalling." EMBO Journal 29, no. 16 (August 18, 2010): 2677–88. http://dx.doi.org/10.1038/emboj.2010.175.

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16

Berridge, Michael J., and Geneviève Dupont. "Spatial and temporal signalling by calcium." Current Opinion in Cell Biology 6, no. 2 (April 1994): 267–74. http://dx.doi.org/10.1016/0955-0674(94)90146-5.

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17

Walmsley, M. E., M. J. Guille, D. Bertwistle, J. C. Smith, J. A. Pizzey, and R. K. Patient. "Negative control of Xenopus GATA-2 by activin and noggin with eventual expression in precursors of the ventral blood islands." Development 120, no. 9 (September 1, 1994): 2519–29. http://dx.doi.org/10.1242/dev.120.9.2519.

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To increase our understanding of haematopoiesis during early vertebrate development, we have studied the expression pattern of the transcription factor GATA-2 in Xenopus embryos, and asked how this is regulated. We show that the blood island precursors of the ventral mesoderm express GATA-2 RNA at neural tube stages, some 5 hours before globin RNA is detected in their derivatives. Prior to this however, GATA-2 is expressed much more widely within the embryo. Maternal transcripts are uniformly distributed, and zygotic transcription is activated during gastrulation throughout ventral and lateral regions of the embryo, with expression highest in the sensorial ectoderm and only weak in the ventral mesoderm. The domain of GATA-2 expression in neurulae outlines the region of the neural plate and suggests a possible wider role in dorsoventral patterning. To identify the signals involved in regulating this pattern of expression, we performed experiments with embryo explants. GATA-2 is activated autonomously in isolated animal caps and this activation is suppressed by the mesoderm-inducing factor activin, but not by FGF. Thus, the down-regulation of GATA-2 observed in the region of the Spemann organiser may be a response to an activin-like signal emanating from the dorsal-vegetal region or Nieuwkoop centre. GATA-2 activation in animal caps and ventral marginal zones was suppressed by co-culturing with dorsal marginal zones, suggesting that a signal from the Spemann organiser is involved in suppression of GATA-2 in the dorsal region of the embryo. Expression of a candidate for this signal, noggin, had the same effect. Taken together, the observations presented here suggest that GATA-2 activation occurs by default in the absence of signals, that the restriction of its expression within the early embryo is controlled by negative signals emanating from the Nieuwkoop centre and the organiser, and that noggin and activin-like molecules play a role in these signalling pathways.
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18

Zahavi, Eitan Erez, Roy Maimon, and Eran Perlson. "Spatial-specific functions in retrograde neuronal signalling." Traffic 18, no. 7 (May 18, 2017): 415–24. http://dx.doi.org/10.1111/tra.12487.

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19

Schwarz-Romond, Thomas, and Stanislaw A. Gorski. "Focus on the Spatial Organization of Signalling." EMBO Journal 29, no. 16 (August 18, 2010): 2675–76. http://dx.doi.org/10.1038/emboj.2010.185.

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20

Bou-Torrent, J., I. Roig-Villanova, and J. Martinez-Garcia. "Spatial regulation of early phytochrome signalling components." Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 146, no. 4 (April 2007): S226. http://dx.doi.org/10.1016/j.cbpa.2007.01.497.

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21

Fulford, Alexander, Nicolas Tapon, and Paulo S. Ribeiro. "Upstairs, downstairs: spatial regulation of Hippo signalling." Current Opinion in Cell Biology 51 (April 2018): 22–32. http://dx.doi.org/10.1016/j.ceb.2017.10.006.

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22

Guryanova, Yelena, Ralph Silva, Anthony J. Short, Paul Skrzypczyk, Nicolas Brunner, and Sandu Popescu. "Exploring the limits of no backwards in time signalling." Quantum 3 (December 9, 2019): 211. http://dx.doi.org/10.22331/q-2019-12-09-211.

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We present an operational and model-independent framework to investigate the concept of no-backwards-in-time signalling. We define no-backwards-in-time signalling conditions, closely related to the spatial no-signalling conditions. These allow for theoretical possibilities in which the future affects the past, nevertheless without signalling backwards in time. This is analogous to non-local but no-signalling spatial correlations. Furthermore, our results shed new light on situations with indefinite causal structure and their connection to quantum theory.
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23

Berridge, Michael J. "Module 6: Spatial and Temporal Aspects of Signalling." Cell Signalling Biology 6 (October 1, 2014): csb0001006. http://dx.doi.org/10.1042/csb0001006.

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24

Redpath, Stephen A., Graham Heieis, and Georgia Perona-Wright. "Spatial regulation of IL-4 signalling in vivo." Cytokine 75, no. 1 (September 2015): 51–56. http://dx.doi.org/10.1016/j.cyto.2015.02.026.

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25

He, Xin-Yu, Ke Sun, Ruo-Shi Xu, Jia-Li Tan, Cai-Xia Pi, Mian Wan, Yi-Ran Peng, Ling Ye, Li-Wei Zheng, and Xue-Dong Zhou. "Spatial signalling mediated by the transforming growth factor-β signalling pathway during tooth formation." International Journal of Oral Science 8, no. 4 (December 2016): 199–204. http://dx.doi.org/10.1038/ijos.2016.45.

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26

COPP, ANDREW J., and ELIZABETH M. C. FISHER. "Abstracts of papers presented at the fifteenth Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 22 and 23 November 2004." Genetical Research 86, no. 3 (December 2005): 233–41. http://dx.doi.org/10.1017/s0016672305007895.

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The Transforming growth factor-β (TGF-β) family control diverse cellular processes and specify cell-fate/differentiation during embryogenesis in vertebrates and invertebrates. Mutations disrupting TGF-β signalling lead to developmental abnormalities and a range of diseases such as cancer. Nodal is a major TGF-β signal, responsible for gastrulation in embryogenesis. Arkadia (Akd) was discovered by mouse gene-trap mutagenesis and encodes a nuclear E3 ubiquitin ligase. Akd allows the Nodal signal to reach its maximum level and Akd-null mice lack mammalian organiser (MO) and mesendodermal tissues. Although Akd RNA is ubiquitously expressed, Akd-null mice lose a subset of Nodal-dependent functions. The specificity of Akd function is therefore most likely to be regulated post-transcriptionally or by co-factors. Akd possesses differentially spliced 5′ untranslated regions (UTRs) and large 3′ UTR. We have employed bioinformatics and developed a reporter system to address Akd post-transcriptional regulation. Akd RNA may initiate from different promoters and 5′ UTR differential splicing, upstream AUGs (uAUGs) and open-reading frames upstream (uORFs) may regulate protein translation. 5′ and 3′ UTRs can interact to either destabilise or decrease translational efficiency of RNA. The nature of this interaction is cell-type and signal level dependent. These data may represent mechanisms by which translational control of Arkadia is achieved and ultimately how TGF-β/Nodal signalling is regulated during embryogenesis.
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Mullineaux, Philip M., Marino Exposito-Rodriguez, Pierre Philippe Laissue, Nicholas Smirnoff, and Eunsook Park. "Spatial chloroplast-to-nucleus signalling involving plastid–nuclear complexes and stromules." Philosophical Transactions of the Royal Society B: Biological Sciences 375, no. 1801 (May 4, 2020): 20190405. http://dx.doi.org/10.1098/rstb.2019.0405.

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Communication between chloroplasts and the nucleus in response to various environmental cues may be mediated by various small molecules. Signalling specificity could be enhanced if the physical contact between these organelles facilitates direct transfer and prevents interference from other subcellular sources of the same molecules. Plant cells have plastid–nuclear complexes, which provide close physical contact between these organelles. Plastid-nuclear complexes have been proposed to facilitate transfer of photosynthesis-derived H 2 O 2 to the nucleus in high light. Stromules (stroma filled tubular plastid extensions) may provide an additional conduit for transfer of a wider range of signalling molecules, including proteins. However, plastid–nuclear complexes and stromules have been hitherto treated as distinct phenomena. We suggest that plastid–nuclear complexes and stromules work in a coordinated manner so that, according to environmental conditions or developmental state, the two modes of connection contribute to varying extents. We hypothesize that this association is dynamic and that there may be a link between plastid–nuclear complexes and the development of stromules. Furthermore, the changes in contact could alter signalling specificity by allowing an extended or different range of signalling molecules to be delivered to the nucleus. This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
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28

Malbon, C. C., J. Tao, E. Shumay, and H. Y. Wang. "AKAP (A-kinase anchoring protein) domains: beads of structure–function on the necklace of G-protein signalling." Biochemical Society Transactions 32, no. 5 (October 26, 2004): 861–64. http://dx.doi.org/10.1042/bst0320861.

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AKAPs (A-kinase anchoring proteins) are members of a diverse family of scaffold proteins that minimally possess a characteristic binding domain for the RI/RII regulatory subunit of protein kinase A and play critical roles in establishing spatial constraints for multivalent signalling assemblies. Especially for G-protein-coupled receptors, the AKAPs provide an organizing centre about which various protein kinases and phosphatases can be assembled to create solid-state signalling devices that can signal, be modulated and trafficked within the cell. The structure of AKAP250 (also known as gravin or AKAP12), based on analyses of milligram quantities of recombinant protein expressed in Escherichia coli, suggests that the AKAP is probably an unordered scaffold, acting as a necklace on which ‘jewels’ of structure–function (e.g. the RII-binding domain) that provide docking sites on which signalling components can be assembled. Recent results suggest that AKAP250 provides not only a ‘tool box’ for assembling signalling elements, but may indeed provide a basis for spatial constraint observed for many signalling paradigms. The spatial dimension of the integration of cell signalling will probably reflect many functions performed by members of the AKAP family.
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29

Jarnæss, E., and K. Taskén. "Spatiotemporal control of cAMP signalling processes by anchored signalling complexes." Biochemical Society Transactions 35, no. 5 (October 25, 2007): 931–37. http://dx.doi.org/10.1042/bst0350931.

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Ligand-induced changes in cAMP concentration vary in duration, amplitude and extension into the cell. cAMP microdomains are shaped by adenylate cyclases that form cAMP as well as PDEs (phosphodiesterases) that degrade cAMP. Various extracellular signals converge on the cAMP/PKA (protein kinase A) pathway through ligand binding to GPCRs (G-protein-coupled receptors) and the cAMP/PKA pathway is therefore tightly regulated on several levels to maintain specificity in the multitude of signal inputs. AKAPs (A-kinase-anchoring proteins) target PKA to specific substrates and distinct subcellular compartments, providing spatial and temporal specificity for mediation of biological effects channelled through the cAMP/PKA pathway. AKAPs also serve as scaffolding proteins that assemble PKA together with signal terminators such as phosphoprotein phosphatases and cAMP-specific PDEs as well as components of other signalling pathways into multiprotein signalling complexes.
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30

Thorn, P. "Spatial aspects of Ca2+ signalling in pancreatic acinar cells." Journal of Experimental Biology 184, no. 1 (November 1, 1993): 129–44. http://dx.doi.org/10.1242/jeb.184.1.129.

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Secretory cells do not only respond to an agonist with a simple rise in [Ca2+]i. It is now clear that complex patterns of [Ca2+]i elevation in terms of space and time are observed in many cell types and that these patterns may be a cellular mechanism for the regulation of different responses. Ca2+ signalling in exocrine cells of the pancreas promotes the secretion of digestive enzymes and fluid. It has been shown that at high concentrations of agonist (acetylcholine or cholecystokinin) the [Ca2+]i response is initiated in the secretory pole of the cell before spreading across the whole cell. This site of initiation of the [Ca2+]i elevation is in the region where exocytotic release of enzymes occurs and is also the site of a Ca(2+)-dependent chloride channel thought to be crucially important for fluid secretion. Lower concentrations of agonist elicit [Ca2+]i oscillations with complex repetitive patterns characteristic of each agonist. At physiological agonist concentrations, we have recently described repetitive short-lasting Ca2+ spikes that are spatially restricted to the secretory pole of the cell. In addition to these spikes, cholecystokinin also promotes slow transient Ca2+ rises that result in a global rise in Ca2+. The inositol trisphosphate (InsP3) receptor plays a crucial role in all of these various agonist responses, most of which can be reproduced by the infusion of InsP3 into the cell. The high InsP3-sensitivity of the secretory pole is postulated to be due to a localization of high-affinity InsP3 receptors. We speculate that in response to cholecystokinin the short-lasting spikes elicit exocytosis from a small ‘available pool’ of vesicles and that the broader oscillations induce both exocytosis and cell changes that involve movement of vesicles into this ‘available pool’.
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31

Carroll, Bernadette. "Spatial regulation of mTORC1 signalling: Beyond the Rag GTPases." Seminars in Cell & Developmental Biology 107 (November 2020): 103–11. http://dx.doi.org/10.1016/j.semcdb.2020.02.007.

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32

Tan, Shawn Zheng Kai, Despina E. Ganella, Alec Lindsay Ward Dick, Jhodie R. Duncan, Emma Ong-Palsson, Ross A. D. Bathgate, Jee Hyun Kim, and Andrew J. Lawrence. "Spatial Learning Requires mGlu5 Signalling in the Dorsal Hippocampus." Neurochemical Research 40, no. 6 (May 10, 2015): 1303–10. http://dx.doi.org/10.1007/s11064-015-1595-0.

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33

Thomas, A. P., D. C. Renard, and T. A. Rooney. "Spatial and temporal organization of calcium signalling in hepatocytes." Cell Calcium 12, no. 2-3 (February 1991): 111–26. http://dx.doi.org/10.1016/0143-4160(91)90013-5.

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34

Mullineaux, P., N. Baker, U. Bechtold, M. Fryer, and W. Davies. "Spatial dependence for H2O2-directed signalling in Arabidopsis leaves." Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 146, no. 4 (April 2007): S260. http://dx.doi.org/10.1016/j.cbpa.2007.01.657.

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35

Zaccolo, Manuela. "Spatial control of cAMP signalling in health and disease." Current Opinion in Pharmacology 11, no. 6 (December 2011): 649–55. http://dx.doi.org/10.1016/j.coph.2011.09.014.

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36

Weaver, Lesley N., and Claire E. Walczak. "Spatial gradients controlling spindle assembly." Biochemical Society Transactions 43, no. 1 (January 26, 2015): 7–12. http://dx.doi.org/10.1042/bst20140243.

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The mitotic spindle is the macromolecular machine utilized to accurately segregate chromosomes in cells. How this self-organized structure assembles is a key aspect of understanding spindle morphogenesis. In the present review, we focus on understanding mechanisms of spindle self-assembly and address how subcellular signalling gradients, such as Ran-GTP and Aurora B, contribute to spindle organization and function.
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37

Hadjivasiliou, Zena, Ginger L. Hunter, and Buzz Baum. "A new mechanism for spatial pattern formation via lateral and protrusion-mediated lateral signalling." Journal of The Royal Society Interface 13, no. 124 (November 2016): 20160484. http://dx.doi.org/10.1098/rsif.2016.0484.

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Tissue organization and patterning are critical during development when genetically identical cells take on different fates. Lateral signalling plays an important role in this process by helping to generate self-organized spatial patterns in an otherwise uniform collection of cells. Recent data suggest that lateral signalling can be mediated both by junctional contacts between neighbouring cells and via cellular protrusions that allow non-neighbouring cells to interact with one another at a distance. However, it remains unclear precisely how signalling mediated by these distinct types of cell–cell contact can physically contribute to the generation of complex patterns without the assistance of diffusible morphogens or pre-patterns. To explore this question, in this work we develop a model of lateral signalling based on a single receptor/ligand pair as exemplified by Notch and Delta. We show that allowing the signalling kinetics to differ at junctional versus protrusion-mediated contacts, an assumption inspired by recent data which show that the cleavage of Notch in several systems requires both Delta binding and the application of mechanical force, permits individual cells to act to promote both lateral activation and lateral inhibition. Strikingly, under this model, in which Delta can sequester Notch, a variety of patterns resembling those typical of reaction–diffusion systems is observed, together with more unusual patterns that arise when we consider changes in signalling kinetics, and in the length and distribution of protrusions. Importantly, these patterns are self-organizing—so that local interactions drive tissue-scale patterning. Together, these data show that protrusions can, in principle, generate different types of patterns in addition to contributing to long-range signalling and to pattern refinement.
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38

Bojar - Fijałkowski, Tomasz. "Report from 3rd Legal Forum of Spatial Economy and Construction 'Special Investment and Construction Acts." Nieruchomości@ 2 (September 30, 2019): 107–10. http://dx.doi.org/10.5604/01.3001.0014.0244.

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The 3rd Legal Forum of Spatial Economy and Construction, entitled 'Special Investment and Construction Acts', was held on 31 May 2019 at the University of Gdańsk. It was organised by the Department of Administrative Law at the Faculty of Law and Administration of the University of Gdańsk. The Chairman of the Scientific Committee of the Forum, and at the same time the originator of this series of Legal Forums on Spatial Economy and Construction has been Tomasz Bąkowski, PhD, professor of the University of Gdańsk, while the Organising Committee was led by Tomasz Bojar-Fijałkowski, PhD. The forum was held under the auspices of the presidents of Gdynia, Sopot and Gdańsk, its sponsor was the Energa Foundation, and its co-organiser was the Foundation for the Development of the University of Gdańsk. The event was attended by over 40 representatives of academic and professional circles representing the largest Polish university centres, as well as administration and judiciary bodies.
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39

Scott, J. D. "Compartmentalized cAMP signalling: a personal perspective." Biochemical Society Transactions 34, no. 4 (July 21, 2006): 465–67. http://dx.doi.org/10.1042/bst0340465.

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Scaffolding proteins create order out of chaos. Multifunctional binding proteins such as the AKAPs (A-kinase-anchoring proteins) oversee the dynamic organization of signalling events by clustering activator proteins with kinases, phosphatases and phosphodiesterases and directing them toward their downstream effectors. This article will focus on the role of AKAPs in the spatial and temporal control of cAMP signalling events.
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40

HANCOCK, John F., and Robert G. PARTON. "Ras plasma membrane signalling platforms." Biochemical Journal 389, no. 1 (June 21, 2005): 1–11. http://dx.doi.org/10.1042/bj20050231.

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The plasma membrane is a complex, dynamic structure that provides platforms for the assembly of many signal transduction pathways. These platforms have the capacity to impose an additional level of regulation on cell signalling networks. In this review, we will consider specifically how Ras proteins interact with the plasma membrane. The focus will be on recent studies that provide novel spatial and dynamic insights into the micro-environments that different Ras proteins utilize for signal transduction. We will correlate these recent studies suggesting Ras proteins might operate within a heterogeneous plasma membrane with earlier biochemical work on Ras signal transduction.
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41

Christen, B., and J. M. Slack. "Spatial response to fibroblast growth factor signalling in Xenopus embryos." Development 126, no. 1 (January 1, 1999): 119–25. http://dx.doi.org/10.1242/dev.126.1.119.

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We have examined the spatial pattern of activation of the extracellular signal-regulated protein kinase (ERK) during Xenopus development, and show that it closely resembles the expression of various fibroblast growth factors (FGFs). Until the tailbud stage of development, all ERK activation domains are sensitive to the dominant negative FGF receptor, showing that activation is generated by endogenous FGF signalling. ERK is not activated by application of other growth factors like BMP4 or activin, nor is endogenous activation blocked by the respective dominant negative receptors. This shows that various domains of FGF expression, including the periblastoporal region and the midbrain-hindbrain boundary, are also sites of FGF signalling in vivo. Wounding induces a transient (<60 minutes) activation of ERK which is not significantly reduced by the dominant negative FGF receptor. An artificial FGF source, created by injection of eFGF mRNA into cleavage stage embryos, provokes ERK activation outside of its injection site over a range of several cell diameters. The range and extent of ERK activation outside the source region is unchanged by co-injection of a dominant negative form of Ras, which blocks ERK-activation within the source. This suggests that FGF protein can diffuse over several cell diameters.
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42

Iancu, Radu V., Gopalakrishnan Ramamurthy, and Robert D. Harvey. "SPATIAL AND TEMPORAL ASPECTS OF cAMP SIGNALLING IN CARDIAC MYOCYTES." Clinical and Experimental Pharmacology and Physiology 35, no. 11 (November 2008): 1343–48. http://dx.doi.org/10.1111/j.1440-1681.2008.05020.x.

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43

Mackenzie, L. "The spatial pattern of atrial cardiomyocyte calcium signalling modulates contraction." Journal of Cell Science 117, no. 26 (December 15, 2004): 6327–37. http://dx.doi.org/10.1242/jcs.01559.

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44

Scales, Timothy ME, and Maddy Parsons. "Spatial and temporal regulation of integrin signalling during cell migration." Current Opinion in Cell Biology 23, no. 5 (October 2011): 562–68. http://dx.doi.org/10.1016/j.ceb.2011.05.008.

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45

Berridge, Michael J. "Calcium signalling remodelling and disease." Biochemical Society Transactions 40, no. 2 (March 21, 2012): 297–309. http://dx.doi.org/10.1042/bst20110766.

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A wide range of Ca2+ signalling systems deliver the spatial and temporal Ca2+ signals necessary to control the specific functions of different cell types. Release of Ca2+ by InsP3 (inositol 1,4,5-trisphosphate) plays a central role in many of these signalling systems. Ongoing transcriptional processes maintain the integrity and stability of these cell-specific signalling systems. However, these homoeostatic systems are highly plastic and can undergo a process of phenotypic remodelling, resulting in the Ca2+ signals being set either too high or too low. Such subtle dysregulation of Ca2+ signals have been linked to some of the major diseases in humans such as cardiac disease, schizophrenia, bipolar disorder and Alzheimer's disease.
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46

Malhó, Rui, Ana Moutinho, Arnold van der Luit, and Anthony J. Trewavas. "Spatial characteristics to calcium signalling; the calcium wave as a basic unit in plant cell calcium signalling." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 353, no. 1374 (September 29, 1998): 1463–73. http://dx.doi.org/10.1098/rstb.1998.0302.

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Many signals that modify plant cell growth and development initiate changes in cytoplasmic Ca 2+ . The subsequent movement of Ca 2+ in the cytoplasm is thought to take place via waves of free Ca 2+ . These waves may be initiated at defined regions of the cell and movement requires release from a reticulated endoplasmic reticulum and the vacuole. The mechanism of wave propagation is outlined and the possible basis of repetitive reticulum wave formation, Ca 2+ oscillations and capacitative Ca 2+ signalling is discussed. Evidence for the presence of Ca 2+ waves in plant cells is outlined, and from studies on raphides it is suggested that the capabilities for capacitative Ca 2+ signalling are also present. The paper finishes with an outline of the possible interrelation between Ca 2+ waves and organelles and describes the intercellular movement of Ca 2+ waves and the relevance of such information communication to plant development.
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47

Mladineo, Ivona, and Jerko Hrabar. "Leukocyte Nucleolus and Anisakis pegreffii—When Falling Apart Means Falling in Place." Genes 11, no. 6 (June 23, 2020): 688. http://dx.doi.org/10.3390/genes11060688.

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The view of the nucleolus as a mere ribosomal factory has been recently expanded, highlighting its essential role in immune and stress-related signalling and orchestrating. It has been shown that the nucleolus structure, formed around nucleolus organiser regions (NORs) and attributed Cajal bodies, is prone to disassembly and reassembly correlated to various physiological and pathological stimuli. To evaluate the effect of parasite stimulus on the structure of the leukocyte nucleolus, we exposed rat peripheral blood mononuclear cells (PBMC) to the crude extract of the nematode A. pegreffii (Anisakidae), and compared the observed changes to the effect of control (RPMI-1640 media), immunosuppressive (MPA) and immunostimulant treatment (bacterial lipopolysaccharide (LPS) and viral analogue polyinosinic:polycytidylic acid (poly I:C)) by confocal microscopy. Poly I:C triggered the most accentuated changes such as nucleolar fragmentation and structural unravelling, LPS induced nucleolus thickening reminiscent of cell activation, while MPA induced disassembly of dense fibrillar and granular components. A. pegreffii crude extract triggered nucleolar segregation, expectedly more enhanced in treatment with a higher dose. This is the first evidence that leukocyte nucleoli already undergo structural changes 12 h post-parasitic stimuli, although these are likely to subside after successful cell activation.
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48

Laurinen, P. I., and L. A. Olzak. "Functional Aspects of Border-Signalling Mechanisms." Perception 25, no. 1_suppl (August 1996): 92. http://dx.doi.org/10.1068/v96l1208.

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Multiple border-signalling mechanisms have been proposed in some models of object segregation. We investigated whether distinct functions of different border mechanisms could be isolated in human psychophysical tasks. The display was a low-spatial-frequency (1.5 cycles deg−1) sinusoidal grating. Two types of centre-surround stimuli were produced by (i) increasing or decreasing the mean luminance of a central patch of the grating to create a signed luminance border (LB), or (ii) by shifting the grating within the central patch 180° to create a sign-reversing border (PSB) without a change in mean luminance. Grating contrast was kept constant at 20%. Observers performed a spatial 2AFC task in each condition. The PSB stimulus served as the comparison stimulus. Test stimuli were either LB or PSB+LB. The mean luminance of the central test patches varied over trials to create border contrasts of −15% to 15% Michelson contrast. In separate sessions, subjects made four types of comparisons: which of the two central areas appeared (1) to differ more in depth from its surround; (2) to have greater modulation contrast of the sinusoid; (3) lighter/darker, (4) to have higher border contrast. Results depended strongly upon test border type and suggested that the mechanism responding to each has a distinct and different perceptual function, and the two may interact. Our results support the hypothesis that surface lightness is calculated by a sign-preserving mechanism, whereas a phase-insensitive mechanism is involved in percepts relating to segregation in depth.
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49

Bolanos-Garcia, Victor M., Qian Wu, Takashi Ochi, Dimitri Y. Chirgadze, Bancinyane Lynn Sibanda, and Tom L. Blundell. "Spatial and temporal organization of multi-protein assemblies: achieving sensitive control in information-rich cell-regulatory systems." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 370, no. 1969 (June 28, 2012): 3023–39. http://dx.doi.org/10.1098/rsta.2011.0268.

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The regulation of cellular processes in living organisms requires signalling systems that have a high signal-to-noise ratio. This is usually achieved by transient, multi-protein complexes that assemble cooperatively. Even in the crowded environment of the cell, such assemblies are unlikely to form by chance, thereby providing a sensitive regulation of cellular processes. Furthermore, selectivity and sensitivity may be achieved by the requirement for concerted folding and binding of previously unfolded components. We illustrate these features by focusing on two essential signalling pathways of eukaryotic cells: first, the monitoring and repair of DNA damage by non-homologous end joining, and second, the mitotic spindle assembly checkpoint, which detects and corrects defective attachments of chromosomes to the kinetochore. We show that multi-protein assemblies moderate the full range of functional complexity and diversity in the two signalling systems. Deciphering the nature of the interactions is central to understanding the mechanisms that control the flow of information in cell signalling and regulation.
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50

Renucci, A., V. Lemarchandel, and F. Rosa. "An activated form of type I serine/threonine kinase receptor TARAM-A reveals a specific signalling pathway involved in fish head organiser formation." Development 122, no. 12 (December 1, 1996): 3735–43. http://dx.doi.org/10.1242/dev.122.12.3735.

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The role of Transforming Growth Factor beta (TGF-beta)-related molecules in axis formation and mesoderm patterning in vertebrates has been extensively documented, but the identity and mechanisms of action of the endogenous molecules remained uncertain. In this study, we isolate a novel serine/threonine kinase type I receptor, TARAM-A, expressed during early zebrafish embryogenesis first ubiquitously and then restricted to dorsal mesoderm during gastrulation. A constitutive form of the receptor is able to induce the most anterior dorsal mesoderm rapidly and to confer an anterior organizing activity. By contrast, the wild-type form is only able to induce a local expansion of the dorsal mesoderm. Thus an activated form of TARAM-A is sufficient to induce dorsoanterior structures and TARAM-A may be activated by dorsally localized signals. Our data suggest the existence in fish of a specific TGF-beta-related pathway for anterior dorsal mesoderm induction, possibly mediated by TARAM-A and activated at the late blastula stage by localized dorsal determinant.
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