scholarly journals CD81 regulates cell migration through its association with Rac GTPase

2013 ◽  
Vol 24 (3) ◽  
pp. 261-273 ◽  
Author(s):  
Emilio Tejera ◽  
Vera Rocha-Perugini ◽  
Soraya López-Martín ◽  
Daniel Pérez-Hernández ◽  
Alexia I. Bachir ◽  
...  
Keyword(s):  
Cell Migration ◽  
Adhesion Formation ◽  
Direct Interaction ◽  
Cytoplasmic Domain ◽  
Small Gtpase ◽  
Rac Gtpase ◽  
Soluble Peptide ◽  
Cross Correlation Analysis ◽  
Focal Adhesion Formation

CD81 is a member of the tetraspanin family that has been described to have a key role in cell migration of tumor and immune cells. To unravel the mechanisms of CD81-regulated cell migration, we performed proteomic analyses that revealed an interaction of the tetraspanin C-terminal domain with the small GTPase Rac. Direct interaction was confirmed biochemically. Moreover, microscopy cross-correlation analysis demonstrated the in situ integration of both molecules into the same molecular complex. Pull-down experiments revealed that CD81-Rac interaction was direct and independent of Rac activation status. Knockdown of CD81 resulted in enhanced protrusion rate, altered focal adhesion formation, and decreased cell migration, correlating with increased active Rac. Reexpression of wild-type CD81, but not its truncated form lacking the C-terminal cytoplasmic domain, rescued these effects. The phenotype of CD81 knockdown cells was mimicked by treatment with a soluble peptide with the C-terminal sequence of the tetraspanin. Our data show that the interaction of Rac with the C-terminal cytoplasmic domain of CD81 is a novel regulatory mechanism of the GTPase activity turnover. Furthermore, they provide a novel mechanism for tetraspanin-dependent regulation of cell motility and open new avenues for tetraspanin-targeted reagents by the use of cell-permeable peptides.

scholarly journals The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell migration

2007 ◽  
Vol 120 (11) ◽  
pp. 1927-1934 ◽  
Author(s):  
Y.-y. Chuang ◽  
A. Valster ◽  
S. J. Coniglio ◽  
J. M. Backer ◽  
M. Symons
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Adhesion Formation ◽  
Focal Adhesion Formation ◽  
Rho Family

α1 Integrin cytoplasmic domain is involved in focal adhesion formation via association with intracellular proteins

2001 ◽  
Vol 356 (1) ◽  
pp. 233-240 ◽  
Author(s):  
Klemens LÖSTER ◽  
Dörte VOSSMEYER ◽  
Werner HOFMANN ◽  
Werner REUTTER ◽  
Kerstin DANKER
Keyword(s):  
Signal Transduction ◽  
Focal Adhesion ◽  
Protein Interactions ◽  
Adhesion Formation ◽  
Focal Adhesions ◽  
Cell Types ◽  
Cytoplasmic Domain ◽  
Integrin Subunit ◽  
Adhesion Receptors ◽  
Focal Adhesion Formation

Integrins are heterodimeric adhesion receptors consisting of α- and β-subunits capable of binding extracellular matrix molecules as well as other adhesion receptors on neighbouring cells. These interactions induce various signal transduction pathways in many cell types, leading to cytoskeletal reorganization, phosphorylation and induction of gene expression. Integrin ligation leads to cytoplasmic protein–protein interactions requiring both integrin cytoplasmic domains, and these domains are initiation points for focal adhesion formation and subsequent signal transduction cascades. In previous studies we have shown that the very short cytoplasmic α1 tail is required for post-ligand events, such as cell spreading as well as actin stress-fibre formation. In the present paper we report that cells lacking the cytoplasmic domain of the α1 integrin subunit are unable to form proper focal adhesions and that phosphorylation on tyrosine residues of focal adhesion components is reduced on α1β1-specific substrates. The α1 cytoplasmic sequence is a specific recognition site for focal adhesion components like paxillin, talin, α-actinin and pp125FAK. It seems to account for α1-specific signalling, since when peptides that mimic the cytoplasmic domain of α1 are transferred into cells, they influence α1β1-specific adhesion, presumably by competing for binding partners. For α1 integrin/protein binding, the conserved Lys-Ile-Gly-Phe-Phe-Lys-Arg motif and, in particular, the two lysine residues, are important.

scholarly journals Acacetin and Pinostrobin Inhibit Malignant Breast Epithelial Cell Adhesion and Focal Adhesion Formation to Attenuate Cell Migration

2020 ◽  
Vol 19 ◽  
pp. 153473542091894 ◽  
Author(s):  
Aaron A. Jones ◽  
Scott Gehler
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Focal Adhesion ◽  
Adhesion Formation ◽  
Breast Epithelial Cell ◽  
Breast Epithelial Cells ◽  
Focal Adhesion Formation ◽  
Malignant Breast ◽  
Breast Epithelial ◽  
Mcf10a Cells

Naturally occurring flavonoids, such as acacetin and pinostrobin, disrupt a wide range of processes during tumor progression, such as cell proliferation, apoptosis, and angiogenesis. Although the antiproliferative and antiapoptotic effects of acacetin and pinostrobin have been studied using various cell lines, relatively little is known about the effects of acacetin and pinostrobin on cancer cell migration and metastasis. For instance, it is unclear whether acacetin or pinostrobin have any effect on breast cancer cell migration or adhesion. In this study, we assessed the effects of acacetin and pinostrobin on malignant MDA-MB-231 and T47D breast epithelial cells and non-tumorigenic MCF10A breast epithelial cells. Our results demonstrate that both acacetin and pinostrobin selectively inhibit the migration of both MDA-MB-231 and T47D cells in a dose-dependent manner while exhibiting blunted effects on MCF10A cells. Interestingly, neither compound had an effect on cell proliferation in any of the 3 cell lines. Furthermore, both acacetin and pinostrobin inhibit MDA-MB-231 and T47D cell adhesion, cell spreading, and focal adhesion formation, but have no significant effect on MCF10A cells. Collectively, these results suggest that both acacetin and pinostrobin selectively inhibit malignant breast epithelial cell migration through attenuation of cell adhesion and focal adhesion formation. These findings indicate that both acacetin and pinostrobin may serve as potential therapeutic options to target breast tumor cell migration during late-stage tumor progression.

scholarly journals Ankyrin repeat domain 28 (ANKRD28), a novel binding partner of DOCK180, promotes cell migration by regulating focal adhesion formation

2009 ◽  
Vol 315 (5) ◽  
pp. 863-876 ◽  
Author(s):  
Mitsuhiro Tachibana ◽  
Etsuko Kiyokawa ◽  
Shigeo Hara ◽  
Shun-ichiro Iemura ◽  
Tohru Natsume ◽  
...  
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Adhesion Formation ◽  
Ankyrin Repeat ◽  
Binding Partner ◽  
Focal Adhesion Formation ◽  
Repeat Domain ◽  
Ankyrin Repeat Domain

scholarly journals Rho kinases regulate corneal epithelial wound healing

2008 ◽  
Vol 295 (2) ◽  
pp. C378-C387 ◽  
Author(s):  
Jia Yin ◽  
Fu-Shin X. Yu
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Cell Migration ◽  
Rho Gtpase ◽  
Adhesion Formation ◽  
Small Gtpase ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing ◽  
Rho Kinases

We have previously shown that Rho small GTPase is required for modulating both cell migration and proliferation through cytoskeleton reorganization and focal adhesion formation in response to wounding. In the present study, we investigated the role of Rho kinases (ROCKs), major effectors of Rho GTPase, in mediating corneal epithelial wound healing. Both ROCK 1 and 2 were expressed and activated in THCE cells, an SV40-immortalized human corneal epithelial cell (HCEC) line, in response to wounding, lysophosphatidic acid, and heparin-binding EGF-like growth factor (HB-EGF) stimulations. The ROCK inhibitor Y-27632 efficiently antagonized ROCK activities without affecting Rho activation in wounded HCECs. Y-27632 promoted basal and HB-EGF-enhanced scratch wound healing and enhanced cell migration and adhesion to matrices, while retarded HB-EGF induced cell proliferation. E-cadherin- and β-catenin-mediated cell-cell junction and actin cytoskeleton organization were disrupted by Y-27632. Y-27632 impaired the formation and maintenance of tight junction barriers indicated by decreased trans-epithelial resistance and disrupted occludin staining. We conclude that ROCK activities enhance cell proliferation, promote epithelial differentiation, but negatively modulate cell migration and cell adhesion and therefore play a role in regulating corneal epithelial wound healing.

scholarly journals Loss of ADAM9 expression impairs β1 integrin endocytosis, focal adhesion formation and cancer cell migration

2017 ◽  
Vol 131 (1) ◽  
pp. jcs205393 ◽  
Author(s):  
Kasper J. Mygind ◽  
Jeanette Schwarz ◽  
Pranshu Sahgal ◽  
Johanna Ivaska ◽  
Marie Kveiborg
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Focal Adhesion ◽  
Adhesion Formation ◽  
Β1 Integrin ◽  
Cancer Cell Migration ◽  
Focal Adhesion Formation
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