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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to

Yu Wang1, Hong Cao, Jing Chen

  • 1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.

Molecular Biology of the Cell
|March 18, 2011
PubMed

Insights

Focal adhesion turnover, crucial for tumor cell migration, involves dynamin (Dyn) recruitment and phosphorylation. A novel Src-FAK-Dyn2 complex mediates integrin endocytosis, driving focal adhesion disassembly.

Area of Science:

  • Cell biology
  • Molecular oncology
  • Biochemistry

Background:

  • Tumor cell migration relies on dynamic focal adhesions (FAs).
  • The mechanisms regulating FA turnover are not fully understood.
  • Dynamin (Dyn), a large GTPase, is implicated in FA dynamics and activated by phosphorylation.

Purpose of the Study:

  • To elucidate the molecular mechanisms regulating focal adhesion turnover.
  • To define the role of dynamin (Dyn) in the context of focal adhesion kinase (FAK) and Src signaling.
  • To identify novel regulators of focal adhesion dynamics during tumor cell migration.

Main Methods:

  • Utilized a novel antibody for phospho-dynamin (pDyn-Tyr-231).
  • Investigated protein-protein interactions using biochemical assays.
  • Employed mutant analysis to assess the functional significance of the Src-FAK-Dyn2 complex.
  • Examined integrin endocytosis via clathrin-dependent pathways.

Main Results:

  • Dynamin 2 (Dyn2) is phosphorylated at FAs by Src kinase.
  • Focal adhesion kinase (FAK) acts as an adaptor, recruiting Dyn2 to FAs for phosphorylation by Src.
  • A trimeric Src-FAK-Dyn2 complex is essential for FA turnover; disruption inhibits disassembly.
  • Phosphorylated Dyn2 drives FA turnover by mediating clathrin-dependent integrin endocytosis.

Conclusions:

  • A novel mechanism for FA turnover is defined, with Dyn2 as a downstream effector of FAK-Src signaling.
  • The Src-FAK-Dyn2 complex plays a critical role in regulating FA dynamics.
  • This pathway provides new insights into the regulation of tumor cell migration.

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