Modulation of cell spreading and cell-substrate adhesion dynamics by dystroglycan

Thompson, Oliver; Moore, C. J.; Hussain, Sadaf-Ahmahni; Kleino, Iivari; Peckham, Michelle; Hohenester, Erhard; Ayscough, Kathryn R.; Saksela, Kalle; Winder, Steve J.

doi:10.1242/jcs.047902

Cited by 53 publications

(58 citation statements)

References 41 publications

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“…A candidate for an additional signaling pathway modulated by Sorbs3 is focal adhesion signaling. Sorbs3 is often localized to, promotes the assembly of and binds to several components of focal adhesions (Kioka et al, 1999;Gehmlich et al, 2007;Thompson et al, 2010). Several integrins, which are extracellular components of focal adhesions, have been implicated in NC migration, and loss of these proteins cause defects in NC development (reviewed by Perris and Perissinotto, 2000).…”

Section: Discussionmentioning

confidence: 99%

Modulation of dorsal root ganglion development by ErbB signaling and the scaffold protein Sorbs3

et al. 2013

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The multipotent cells of the vertebrate neural crest (NC) arise at the dorsal aspect of the neural tube, then migrate throughout the developing embryo and differentiate into diverse cell types, including the sensory neurons and glia of the dorsal root ganglia (DRG). As multiple cell types are derived from this lineage, it is ideal for examining mechanisms of fate restriction during development. We have isolated a mutant, ouchless, that specifically fails to develop DRG neurons, although other NC derivatives develop normally. This mutation affects the expression of Sorbs3, a scaffold protein known to interact with proteins involved in focal adhesions and several signaling pathways. ouchless mutants share some phenotypic similarities with mutants in ErbB receptors, EGFR homologs that are implicated in diverse developmental processes and associated with several cancers; and ouchless interacts genetically with an allele of erbb3 in DRG neurogenesis. However, the defect in ouchless DRG neurogenesis is distinct from ErbB loss of function in that it is not associated with a loss of glia. Both ouchless and neurogenin1 heterozygous fish are sensitized to the effects of ErbB chemical inhibitors, which block the development of DRG in a dose-dependent manner. Inhibitors of MEK show similar effects on DRG neurogenesis. We propose a model in which Sorbs3 helps to integrate ErbB signals to promote DRG neurogenesis through the activation of MAPK and upregulation of neurogenin1.

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Section: Discussionmentioning

confidence: 99%

Modulation of dorsal root ganglion development by ErbB signaling and the scaffold protein Sorbs3

et al. 2013

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“…Dystroglycan might also promote RhoGTPAse activation in SCs as it does in muscles (Thompson et al, 2010). The amount of active, GTP-bound Rac1, Cdc42 and RhoA in nerves from dystroglycan mutant and controls at P3 and P28 was similar (Fig.…”

Section: Dystroglycan Does Not Regulate Rac1 Cdc42 or Rhoamentioning

confidence: 78%

Non-redundant function of dystroglycan and β1 integrins in radial sorting of axons

Berti¹,

Bartesaghi²,

Ghidinelli³

et al. 2011

Development

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SUMMARYRadial sorting allows the segregation of axons by a single Schwann cell (SC) and is a prerequisite for myelination during peripheral nerve development. Radial sorting is impaired in models of human diseases, congenital muscular dystrophy (MDC) 1A, MDC1D and Fukuyama, owing to loss-of-function mutations in the genes coding for laminin 2, Large or fukutin glycosyltransferases, respectively. It is not clear which receptor(s) are activated by laminin 211, or glycosylated by Large and fukutin during sorting. Candidates are 1 integrins, because their absence phenocopies laminin and glycosyltransferase deficiency, but the topography of the phenotypes is different and 1 integrins are not substrates for Large and fukutin. By contrast, deletion of the Large and fukutin substrate dystroglycan does not result in radial sorting defects. Here, we show that absence of dystroglycan in a specific genetic background causes sorting defects with topography identical to that of laminin 211 mutants, and recapitulating the MDC1A, MDC1D and Fukuyama phenotypes. By epistasis studies in mice lacking one or both receptors in SCs, we show that only absence of 1 integrins impairs proliferation and survival, and arrests radial sorting at early stages, that 1 integrins and dystroglycan activate different pathways, and that the absence of both molecules is synergistic. Thus, the function of dystroglycan and 1 integrins is not redundant, but is sequential. These data identify dystroglycan as a functional laminin 211 receptor during axonal sorting and the key substrate relevant to the pathogenesis of glycosyltransferase congenital muscular dystrophies.

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“…Cell adherence to other cells and to its substrate affects cell shape and cellular organization in the tissue (Thompson et al 2010). Adhesion of a cell to its ECM starts with the recognition of particular domains in adhesive proteins of the matrix, such as laminin, fibrinogen, fibronectin, vitronectin, and some collagens, by structurally relatedplasma membrane receptors, called integrins.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

Jalali

Tafazzoli-Shadpour

Haghighipour

et al. 2015

Cell Communication & Adhesion

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Although substrate stiffness has been previously reported to affect various cellular aspects, such as morphology, migration, viability, growth, and cytoskeletal structure, its influence on cell adherence has not been well examined. Here, we prepared three soft, medium, and hard polyacrylamide (PAAM) substrates and utilized AFM to study substrate elasticity and also the adhesion and mechanical properties of endothelial cells in response to changing substrate stiffness. Maximum detachment force and cell stiffness were increased with increasing substrate stiffness. Maximum detachment force values were 0.28 ± 0.14, 0.94 ± 0.27, and 1.99 ± 0.59 nN while Young's moduli of cells were 218. 85 ± 38.73, 385.58 ± 131.67, and 933.20 ± 428.92 Pa for soft, medium, and hard substrates, respectively. Human umbilical vein endothelial cells (HUVECs) showed round to more spread shapes on soft to hard substrates, with the most organized and elongated actin structure on the hard hydrogel. Our results confirm the importance of substrate stiffness in regulating cell mechanics and adhesion for a successful cell therapy. ARTICLE HISTORY

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Modulation of cell spreading and cell-substrate adhesion dynamics by dystroglycan

Cited by 53 publications

References 41 publications

Modulation of dorsal root ganglion development by ErbB signaling and the scaffold protein Sorbs3

Modulation of dorsal root ganglion development by ErbB signaling and the scaffold protein Sorbs3

Non-redundant function of dystroglycan and β1 integrins in radial sorting of axons

Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

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