Dataset Information

The small GTPase RhoG regulates microtubule-mediated focal adhesion disassembly.

ABSTRACT: Focal adhesions (FA) are a complex network of proteins that allow the cell to form physical contacts with the extracellular matrix (ECM). FA assemble and disassemble in a dynamic process, orchestrated by a variety of cellular components. However, the underlying mechanisms that regulate adhesion turnover remain poorly understood. Here we show that RhoG, a Rho GTPase related to Rac, modulates FA dynamics. When RhoG expression is silenced, FA are more stable and live longer, resulting in an increase in the number and size of adhesions, which are also more mature and fibrillar-like. Silencing RhoG also increases the number and thickness of stress fibers, which are sensitive to blebbistatin, suggesting contractility is increased. The molecular mechanism by which RhoG regulates adhesion turnover is yet to be characterized, but our results demonstrate that RhoG plays a role in the regulation of microtubule-mediated FA disassembly.

SUBMITTER: Zinn A

PROVIDER: S-EPMC6435757 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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The small GTPase RhoG regulates microtubule-mediated focal adhesion disassembly.

Zinn Ashtyn A Goicoechea Silvia M SM Kreider-Letterman Gabriel G Maity Debonil D Awadia Sahezeel S Cedeno-Rosario Luis L Chen Yun Y Garcia-Mata Rafael R

Scientific reports 20190326 1

Focal adhesions (FA) are a complex network of proteins that allow the cell to form physical contacts with the extracellular matrix (ECM). FA assemble and disassemble in a dynamic process, orchestrated by a variety of cellular components. However, the underlying mechanisms that regulate adhesion turnover remain poorly understood. Here we show that RhoG, a Rho GTPase related to Rac, modulates FA dynamics. When RhoG expression is silenced, FA are more stable and live longer, resulting in an increas ...[more]

PMID: 30914742

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Project description:The survival of endothelial cells is dependent on interactions between the matrix and integrins mediated through focal adhesions. Focal adhesion kinase (FAK) is thought to play a key role in maintaining focal adhesion function and cell survival, whereas caspase-mediated FAK proteolysis is implicated in focal adhesion disassembly during apoptosis. We examined the relationship between changes in FAK phosphorylation and proteolysis during apoptosis of primary porcine aortic endothelial cells (PAEC) induced by staurosporine, a widely used apoptogenic agent in diverse cell types. Staurosporine-induced PAEC apoptosis was detected after 1 h and was preceded by disruption and loss of FAK localization to focal adhesions within a few minutes, whereas staurosporine-induced cleavage of FAK occurred only after 8-24 h. Staurosporine induced a very rapid dephosphorylation of FAK at Tyr(861) and Tyr(397) and caused dissociation of phosphorylated FAK from focal adhesions as early as 30 s. The effect of staurosporine was very potent with striking inhibition of Tyr(861) and Tyr(397) phosphorylation and focal adhesion disruption occurring in the range 10-100 nM. Selective inhibition of a known target of staurosporine, protein kinase C, using GF109203X, and of phosphoinositide 3'-kinase using wortmannin, did not reduce FAK tyrosine phosphorylation at Tyr(861) and Tyr(397), or cause disruption of focal adhesions. Cycloheximide, the protein synthesis inhibitor, induced PAEC apoptosis more slowly than staurosporine, but did not induce FAK dephosphorylation or rapid focal adhesion disruption, and instead caused a slower loss of focal adhesions and a marked increase in FAK proteolysis. These studies show that FAK dephosphorylation and focal adhesion disassembly are very early events mediating the onset of staurosporine-induced endothelial cell apoptosis and are dissociated from FAK proteolysis. Cycloheximide induces apoptosis through a pathway involving FAK proteolysis without dephosphorylation.

Dataset Information

The small GTPase RhoG regulates microtubule-mediated focal adhesion disassembly.

Publications

The small GTPase RhoG regulates microtubule-mediated focal adhesion disassembly.

Similar Datasets

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