Cell Biology

Forced to Become Focal Adhesions

Science's STKE  19 Jun 2001:
Vol. 2001, Issue 87, pp. tw2
DOI: 10.1126/stke.2001.87.tw2

What is the signal that lets the cell know that it is time for the first type of cell-surface contact structure, the focal complex, to become a focal adhesion with stress fibers? Signaling through the guanosine triphosphatase (GTPase) Rho is important for focal focal adhesion formation. Rho stimulates the Rho-associated kinase, ROCK, which promotes myosin II-controlled contractility. Rho also activates the mammalian homolog of Drosophila Diaphanous protein, mDia1, which participates in cytoskeletal rearrangement in focal adhesion formation. Riveline et al. have addressed the hypothesis that mechanical force initiates this transformation. They used a micropipette micromanipulation technique to apply mechanical force to localized areas of cultured cells (NIH 3T3 or SV-80 cells). Locally applied mechanical force induced the formation of focal adhesions (detected by paxillin or vinculin labeled with green fluorescent protein). These mechanically induced focal adhesions were dependent on the actin cytoskeleton and engagement of integrin receptors with the substrate, but were independent of actin-myosin-mediated cell contraction. Inhibition of Rho activity blocked the formation of focal adhesions by local force, and this block could be overcome by expression of constitutively active forms of mDia1; however, the activity of the downstream target ROCK was dispensable. Thus, the authors propose that conversion to a focal adhesion involves two steps following integrin engagement and activation of Rho: (i) the production of force through the activation of myosin II by ROCK, and (ii) the activation of mDia1, which leads to the formation of stress fibers. Externally applied mechanical force bypasses the first step.

D. Riveline, E. Zamir, N. Q. Balaban, U. S. Schwarz, T. Ishizaki, S. Narumiya, Z. Kam, B. Geiger, A. D. Bershadsky, Focal contacts act as mechanosensors: Externally applied local mechanical force induces growth of focal contacts by an mDia-dependent and ROCK-independent mechanism. J. Cell Biol. 153, 1175-1185 (2001). [Abstract] [Full Text]