TSC2 Modulates Actin Cytoskeleton and Focal Adhesion Through TSC1-Binding Domain and the Rac1 GTPase

Authors

Elena Goncharova, University of Pennsylvania
Dmitry Goncharov, University of Pennsylvania
Daniel J. Noonan, University of KentuckyFollow
Vera P Krymskaya, University of Pennsylvania

Abstract

Tuberous sclerosis complex (TSC) 1 and TSC2 are thought to be involved in protein translational regulation and cell growth, and loss of their function is a cause of TSC and lymphangioleiomyomatosis (LAM). However, TSC1 also activates Rho and regulates cell adhesion. We found that TSC2 modulates actin dynamics and cell adhesion and the TSC1-binding domain (TSC2-HBD) is essential for this function of TSC2. Expression of TSC2 or TSC2-HBD in TSC2-/- cells promoted Rac1 activation, inhibition of Rho, stress fiber disassembly, and focal adhesion remodeling. The down-regulation of TSC1 with TSC1 siRNA in TSC2-/- cells activated Rac1 and induced loss of stress fibers. Our data indicate that TSC1 inhibits Rac1 and TSC2 blocks this activity of TSC1. Because TSC1 and TSC2 regulate Rho and Rac1, whose activities are interconnected in a reciprocal fashion, loss of either TSC1 or TSC2 function may result in the deregulation of cell motility and adhesion, which are associated with the pathobiology of TSC and LAM.

Document Type

Article

Publication Date

12-20-2004

Notes/Citation Information

Published in The Journal of Cell Biology, v. 167, no. 6, p. 1171-1182.

© 2004 Rockefeller University Press

Beginning six months after publication, RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.

Digital Object Identifier (DOI)

http://dx.doi.org/10.1083/jcb.200405130

Repository Citation

Goncharova, Elena; Goncharov, Dmitry; Noonan, Daniel J.; and Krymskaya, Vera P, "TSC2 Modulates Actin Cytoskeleton and Focal Adhesion Through TSC1-Binding Domain and the Rac1 GTPase" (2004). Molecular and Cellular Biochemistry Faculty Publications. 57.
https://uknowledge.uky.edu/biochem_facpub/57