Plexin signaling hampers integrin‐based adhesion, leading to Rho‐kinase independent cell rounding, and inhibiting lamellipodia extension and cell motility

Barberis, Davide; Artigiani, Stefania; Casazza, Andrea; Corso, Simona; Giordano, Silvia; Love, Christopher; Jones, E Y; Comoglio, Paolo M.; Tamagnone, Luca

doi:10.1096/fj.03-0957fje

Cited by 112 publications

(142 citation statements)

References 60 publications

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“…Expression of Plexin-B1 in fibroblasts inhibits integrin-dependent cell adhesion to the ECM protein fibronectin (22). This inhibition is due to activation of the intrinsic GTPase activity of R-Ras by Plexin-B1, resulting in R-Ras inactivation and a decrease in integrin-based cell adhesion (9).…”

Section: Resultsmentioning

confidence: 99%

Plexin-B1 mutations in prostate cancer

Wong

Nitkunan

Oinuma

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Semaphorins are a large class of secreted or membrane-associated proteins that act as chemotactic cues for cell movement via their transmembrane receptors, plexins. We hypothesized that the function of the semaphorin signaling pathway in the control of cell migration could be harnessed by cancer cells during invasion and metastasis. We now report 13 somatic missense mutations in the cytoplasmic domain of the Plexin-B1 gene. Mutations were found in 89% (8 of 9) of prostate cancer bone metastases, in 41% (7 of 17) of lymph node metastases, and in 46% (41 of 89) of primary cancers. Forty percent of prostate cancers contained the same mutation. Overexpression of the Plexin-B1 protein was found in the majority of primary tumors. The mutations hinder Rac and R-Ras binding and R-RasGAP activity, resulting in an increase in cell motility, invasion, adhesion, and lamellipodia extension. These results identify a key role for Plexin-B1 and the semaphorin signaling pathway it mediates in prostate cancer.adhesion ͉ migration ͉ R-Ras ͉ Rac ͉ semaphorin

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Section: Resultsmentioning

confidence: 99%

Plexin-B1 mutations in prostate cancer

Wong

Nitkunan

Oinuma

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Plexins were also initially identified as cell surface molecules, and their exogenous expression on the surface of L cells promotes cell adhesion via a homophilic binding mechanism (Ohta et al, 1995; Fujisawa et al, 1997). Subsequent studies have shown that Sema4D activation of PlexinB1 and PlexinA1 hinders cell attachment to adhesive substrates, resulting in cell collapse and inhibition of cell migration (Barberis et al, 2004). …”

Section: Discussionmentioning

confidence: 99%

Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice

Andrews

Davidson

Tamamaki

et al. 2015

J of Comparative Neurology

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Cortical interneurons are generated predominantly in the medial ganglionic eminence (MGE) and migrate through the ventral and dorsal telencephalon before taking their final positions within the developing cortical plate. Previously we demonstrated that interneurons from Robo1 knockout (Robo1−/−) mice contain reduced levels of neuropilin 1 (Nrp1) and PlexinA1 receptors, rendering them less responsive to the chemorepulsive actions of semaphorin ligands expressed in the striatum and affecting their course of migration (Hernandez‐Miranda et al. [2011] J. Neurosci. 31:6174–6187). Earlier studies have highlighted the importance of Nrp1 and Nrp2 in interneuron migration, and here we assess the role of PlexinA1 in this process. We observed significantly fewer cells expressing the interneuron markers Gad67 and Lhx6 in the cortex of PlexinA1 −/− mice compared with wild‐type littermates at E14.5 and E18.5. Although the level of apoptosis was similar in the mutant and control forebrain, proliferation was significantly reduced in the former. Furthermore, progenitor cells in the MGE of PlexinA1 −/− mice appeared to be poorly anchored to the ventricular surface and showed reduced adhesive properties, which may account for the observed reduction in proliferation. Together our data uncover a novel role for PlexinA1 in forebrain development. J. Comp. Neurol. 524:518–534, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

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“…They are divided into four subfamilies, plexins A to D, according to the structure of their extracellular domain. Previous studies have shown that in neurons or cell lines, plexin engagement by semaphorins induces rearrangement of the actin cytoskeleton and inhibits integrinmediated cell adhesion, which leads to cellular retraction [13,14]. Although semaphorins and plexins are predominantly expressed in the nervous system, they can also be found in other tissues such as the vascular system [15] or the immune system [16].…”

Section: Introductionmentioning

confidence: 99%

Poxvirus semaphorin A39R inhibits phagocytosis by dendritic cells and neutrophils

2005

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The poxvirus A39R protein is a member of the semaphorin family that binds to Plexin C1, a molecule expressed on neutrophils and dendritic cells (DC). We previously showed that binding of A39R to Plexin C1 induces local rearrangement of the actin cytoskeleton and inhibits integrin-mediated adhesion, leading to cell retraction. As phagocytosis is dependent on both cytoskeleton integrity and integrin function, we tested the effect of A39R on DC and neutrophil phagocytosis. We found that A39R treatment strongly inhibits phagocytosis by DC and neutrophils in vitro in a Plexin C1-dependent fashion. Moreover, A39R treatment inhibited the capacity of CD8a + DC to take up apoptotic bodies in vivo. As a consequence, A39R impaired the ability of CD8a + DC to cross-prime CD8 + T cells ex vivo. In contrast, A39R had no effect on direct priming of CD8 + T cells by peptide-pulsed CD8a + DC in vitro. These results suggest that poxviruses may use semaphorin homologs as a means to evade the immune system.

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Plexin signaling hampers integrin‐based adhesion, leading to Rho‐kinase independent cell rounding, and inhibiting lamellipodia extension and cell motility

Cited by 112 publications

References 60 publications

Plexin-B1 mutations in prostate cancer

Plexin-B1 mutations in prostate cancer

Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice

Poxvirus semaphorin A39R inhibits phagocytosis by dendritic cells and neutrophils

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