Molecular mechanisms for focal adhesion assembly through regulation of protein–protein interactions

Gilmore, Andrew; Burridge, Keith

doi:10.1016/s0969-2126(96)00069-x

Cited by 77 publications

(51 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3A and Fig. 4A,B), probably as a consequence of the loss of 'inside-out' signaling, whereby intracellular myosin-II-dependent contractility enhances the assembly of focal adhesions Gilmore and Burridge, 1996;Ginsberg et al, 2005). We found that microtubule depolymerization allows these residual focal complexes and traction forces to recover partially.…”

Section: Discussionmentioning

confidence: 69%

Microtubule depolymerization induces traction force increase through two distinct pathways

Rape

Guo

Wang

2011

Journal of Cell Science

View full text Add to dashboard Cite

SummaryTraction forces increase after microtubule depolymerization; however, the signaling mechanisms underlying this, in particular the dependence upon myosin II, remain unclear. We investigated the mechanism of traction force increase after nocodazole-induced microtubule depolymerization by applying traction force microscopy to cells cultured on micropatterned polyacrylamide hydrogels to obtain samples of homogeneous shape and size. Control cells and cells treated with a focal adhesion kinase (FAK) inhibitor showed similar increases in traction forces, indicating that the response is independent of FAK. Surprisingly, pharmacological inhibition of myosin II did not prevent the increase of residual traction forces upon nocodazole treatment. This increase was abolished upon pharmacological inhibition of FAK. These results suggest two distinct pathways for the regulation of traction forces. First, microtubule depolymerization activates a myosin-II-dependent mechanism through a FAK-independent pathway. Second, microtubule depolymerization also enhances traction forces through a myosin-II-independent, FAK-regulated pathway. Traction forces are therefore regulated by a complex network of complementary signals and force-generating mechanisms.

show abstract

Section: Discussionmentioning

confidence: 69%

Microtubule depolymerization induces traction force increase through two distinct pathways

Rape

Guo

Wang

2011

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Paxillin, along with other focal adhesion constituents such as FAK, are considered essential integrin-associated signalling molecules. Phosphorylation of paxillin and FAK coordinate the formation of focal adhesions and stress fibres, creating a platform for transduction of a variety of signalling information to specific targets via hierarchical and synergistic molecular interactions (Gilmore & Burridge, 1996;Schlaepfer et al, 1999;Turner, 2000;Schaller, 2001). We have investigated the temporal and spatial distribution of paxillin and FAK, along with microfilament and microtubule components of the GEC cytoskeleton, following infection with P. gingivalis.…”

Section: Discussionmentioning

confidence: 99%

Gingival epithelial cell signalling and cytoskeletal responses to Porphyromonas gingivalis invasion

et al. 2003

View full text Add to dashboard Cite

Porphyromonas gingivalis, an oral pathogen, can internalize within primary gingival epithelial cells (GECs) through an invasion mechanism mediated by interactions between P. gingivalis fimbriae and integrins on the surface of the GECs. Fimbriae-integrin-based signalling events were studied by fluorescence microscopy, and the subcellular localization of integrin-associated signalling molecules paxillin and focal adhesion kinase (FAK), and the architecture of the actin and microtubule cytoskeleton were examined. GECs infected with P. gingivalis for 30 min demonstrated significant redistribution of paxillin and FAK from the cytosol to cell peripheries and assembly into focal adhesion complexes. In contrast, a fimbriae-deficient mutant of P. gingivalis did not contribute substantially to activation of paxillin or FAK. After 24 h, the majority of paxillin and FAK had returned to the cytoplasm with significant co-localization with P. gingivalis in the perinuclear region. Wild-type P. gingivalis induced nucleation of actin filaments forming microspike-like protrusions and long stable microfilaments distributed throughout the cells. Fimbriae mutants promoted a rich cortical actin meshwork accompanied by membrane ruffling dispersed along the cell membrane. Remarkable disassembly and nucleation of the actin and microtubule filamentous network was observed following 24 h infection with either wild-type or fimbriae-deficient mutants of P. gingivalis. The results show that fimbriated P. gingivalis cells induce formation of integrin-associated focal adhesions with subsequent remodelling of the actin and tubulin cytoskeleton.

show abstract

“…Integrins are a major family of transmembrane proteins that mediate cellular association with ECM. The engagement of cell surface integrins with ligands leads to recruitment of a number of intracellular proteins to specialized sites of the cytoplasmic face in focal adhesions (4). Although the molecular mechanism of integrin-mediated signal transduction is not well defined, tyrosine phosphorylation of several cytoplasmic proteins, including focal adhesion kinase (FAK), paxillin, tensin, and Cas, is a critical biochemical aspect in this process (5)(6)(7)(8)(9)(10).…”

Section: Cell Adhesion To Extracellular Matrix (Ecm)mentioning

confidence: 99%

Protein-tyrosine Phosphatase Shp-2 Regulates Cell Spreading, Migration, and Focal Adhesion

Yu¹,

Qu²,

Henegariu³

et al. 1998

Journal of Biological Chemistry

364

337

View full text Add to dashboard Cite

Shp-2, a widely expressed cytoplasmic tyrosine phosphatase with two SH2 domains, is believed to participate in signal relay downstream of growth factor receptors. We show here that this phosphatase also plays an important role in the control of cell spreading, migration, and cytoskeletal architecture. Fibroblast cells lacking a functional Shp-2 were impaired in their ability to spread and migrate on fibronectin compared with wild-type cells. Furthermore, Shp-2 mutant cells displayed an increased number of focal adhesions and condensed F-actin aggregation at the cell periphery, properties reminiscent of focal adhesion kinase (FAK)-deficient cells. This is consistent with our previous observations in vivo that mice homozygous for the Shp-2 mutation died at midgestation with similar phenotype to FAK and fibronectin-deficient embryos, having severe defects in mesodermal patterning, particularly the truncation of posterior structures. Biochemical analysis demonstrated that FAK dephosphorylation was significantly reduced in Shp-2 mutant cells in suspension. Furthermore, regulated association of Src SH2 domain with FAK and paxillin during cell attachment and detachment on fibronectin was disrupted in Shp-2 mutant cells. This report defines a unique role of the Shp-2 tyrosine phosphatase in cell motility, which might guide the design of a new strategy for pharmaceutical interference of tumor metastasis.

show abstract

Molecular mechanisms for focal adhesion assembly through regulation of protein–protein interactions

Abstract: Focal adhesions provide a useful model for studying cell/extracellular matrix interactions and the subsequent cytoskeletal reorganization. Recent advances have suggested potential mechanisms by which cells may regulate focal adhesion assembly following integrin-mediated cell adhesion.

Cited by 77 publications

References 36 publications

Microtubule depolymerization induces traction force increase through two distinct pathways

Microtubule depolymerization induces traction force increase through two distinct pathways

Gingival epithelial cell signalling and cytoskeletal responses to Porphyromonas gingivalis invasion

Protein-tyrosine Phosphatase Shp-2 Regulates Cell Spreading, Migration, and Focal Adhesion

Contact Info

Product

Resources

About