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Extracellular Cues (extracellular + cue)
Selected AbstractsSrc-dependent phosphorylation of Scar1 promotes its association with the Arp2/3 complexCYTOSKELETON, Issue 1 2006Hazel Ardern Abstract The WAVE/Scar proteins regulate actin polymerisation at the leading edge of motile cells via activation of the Arp2/3 complex in response to extracellular cues. Within cells they form part of a pentameric complex that is thought to regulate their ability to interact and activate the Arp2/3 complex. However, the exact mechanism for this is not known. We set out to assess whether phosphorylation of Scar1 by the non-receptor tyrosine kinase Src may influence the function of Scar1 and its ability to regulate Arp2/3-mediated actin polymerisation. We show that Scar1 is phosphorylated by Src in vitro and in vivo and identify tyrosine 125 as the major site in Scar1 to be phosphorylated in cells. Src-dependent phosphorylation of Scar1 on tyrosine 125 enhances its ability to bind to the Arp2/3 complex and regulates its ability to control actin polymerisation in cells. Thus, Src may act as an intermediary to regulate the activity of the Arp2/3 complex in response to external stimuli, via modulation of its interaction with WAVE/Scar proteins. Cell Motil. Cytoskeleton, 2006. © 2005 Wiley-Liss, Inc. [source] The Hydra polyp: Nothing but an active stem cell communityDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 1 2010Thomas C. G. Bosch Hydra is a powerful stem cell model because its potential immortality and extensive regeneration capacity is due to the presence of three distinct stem cell lineages. All three lineages conform to a well-defined spatial distribution across the whole body column of the polyp. Stem cell function in Hydra is controlled by extracellular cues and intrinsic genetic programs. This review focuses on the elusive stem cell niche of the epithelial layers. Based on a comparison of the differences between, and commonalities among, stem cells and stem cell niches in Hydra and other invertebrates and vertebrates, we propose that the whole body column of the polyp may be considered a stem cell "niche" in which stem cell populations are established and signals ensuring the proper balance between stem cells and progenitor cells are integrated. We show that, at over 500 million years old, Hydra offers an early glimpse of the regulatory potential of stem cell niches. [source] Astrocytes promote neurogenesis from oligodendrocyte precursor cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006P. M. Gaughwin Abstract The oligodendrocyte precursor cell (OPC) has until recently been regarded as a lineage-restricted precursor cell. Considerable interest has been generated by reports suggesting that OPCs may possess a wider differentiation potential than previously assumed and thus be considered a multipotential stem cell. This study examined the neuronal differentiation potential of rat, postnatal cortical OPCs in response to extracellular cues in vitro and in vivo. OPCs did not exhibit intrinsic neuronal potential and were restricted to oligodendrocyte lineage potential following treatment with the neural precursor mitogen fibroblast growth factor 2. In contrast, a postnatal hippocampal astrocyte-derived signal(s) is sufficient to induce functional neuronal differentiation of cortical OPCs in vitro in population and single cell studies. Co-treatment with Noggin, a bone morphogenetic protein antagonist, did not attenuate neuronal differentiation. Following transplantation to the adult rat hippocampus, cortical OPCs expressed doublecortin, a neuroblast-associated marker. The present findings show that hippocampal, astrocyte-derived signals can induce the neuronal differentiation of OPCs through a Noggin-independent mechanism. [source] A new era for small molecule screening: from new targets, such as JAK2 V617F, to complex cellular screensJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2009Stefan N. ConstantinescuArticle first published online: 21 JAN 200 Traditionally reserved to research and development in pharmaceutical companies, screening of small molecule libraries is rapidly becoming an approach undertaken by academic laboratories. Novel cellular assays, sensitive systems to probe function, emerging new molecular targets are just some of the reasons explaining this shift. Targets of small molecules identified in cellular screens begin to be amenable to identification by elegant genetic approaches, such as probing toxicity of candidate small molecules on libraries of genetically modified yeast strains. Several new targets, such as JAK2 V617F, an activated JAK2 (Janus Kinase 2) mutant genetically associated with the majority of human myeloproliferative neoplasms, are being actively pursued. In this Review Series, we will learn how libraries of small molecules are harnessed to identify novel molecules, that alone or in combination, have the ability to alter cell fate, cell signalling, gene expression or response to extracellular cues. [source] Signaling mechanisms that regulate actin-based motility processes in the nervous systemJOURNAL OF NEUROCHEMISTRY, Issue 3 2002Gary Meyer Abstract Actin-based motility is critical for nervous system development. Both the migration of neurons and the extension of neurites require organized actin polymerization to push the cell membrane forward. Numerous extracellular stimulants of motility and axon guidance cues regulate actin-based motility through the rho GTPases (rho, rac, and cdc42). The rho GTPases reorganize the actin cytoskeleton, leading to stress fiber, filopodium, or lamellipodium formation. The activity of the rho GTPases is regulated by a variety of proteins that either stimulate GTP uptake (activation) or hydrolysis (inactivation). These proteins potentially link extracellular signals to the activation state of rho GTPases. Effectors downstream of the rho GTPases that directly influence actin polymerization have been identified and are involved in neurite development. The Arp2/3 complex nucleates the formation of new actin branches that extend the membrane forward. Ena/VASP proteins can cause the formation of longer actin filaments, characteristic of growth cone actin morphology, by preventing the capping of barbed ends. Actin-depolymerizing factor (ADF)/cofilin depolymerizes and severs actin branches in older parts of the actin meshwork, freeing monomers to be re-incorporated into actively growing filaments. The signaling mechanisms by which extracellular cues that guide axons to their targets lead to direct effects on actin filament dynamics are becoming better understood. [source] Signal Processing during Developmental Multicellular PatterningBIOTECHNOLOGY PROGRESS, Issue 1 2008Claudiu A. Giurumescu Developing design strategies for tissue engineering and regenerative medicine is limited by our nascent understanding of how cell populations "self-organize" into multicellular structures on synthetic scaffolds. Mechanistic insights can be gleaned from the quantitative analysis of biomolecular signals that drive multicellular patterning during the natural processes of embryonic and adult development. This review describes three critical layers of signal processing that govern multicellular patterning: spatiotemporal presentation of extracellular cues, intracellular signaling networks that mediate crosstalk among extracellular cues, and finally, intranuclear signal integration at the level of transcriptional regulation. At every level in this hierarchy, the quantitative attributes of signals have a profound impact on patterning. We discuss how experiments and mathematical models are being used to uncover these quantitative features and their impact on multicellular phenotype. [source] | ||||||||||