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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

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A phosphorylation switch controls the spatiotemporal activation of Rho GTPases in directional cell migration

Xuan Cao1, Tomonori Kaneko2, Jenny S Li3

  • 11] Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada N6A 5C1 [2] Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Nature Communications
|July 14, 2015
PubMed

Insights

A novel molecular switch involving DLC1, TNS3, PTEN, and PI3K controls cell migration. This mechanism, driven by growth factors like EGF and PDGF, precisely activates Rac1 and RhoA for directional movement.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Cancer Research

Background:

  • Cell migration is crucial for development and disease, but its molecular regulation remains incompletely understood.
  • Growth factor-induced cell motility requires precise spatiotemporal control of key signaling pathways.

Purpose of the Study:

  • To elucidate the molecular mechanism controlling directional cell migration.
  • To identify the signaling components responsible for spatiotemporal activation of small GTPases Rac1 and RhoA.

Main Methods:

  • Investigated the roles of deleted in liver cancer 1 (DLC1), tensin-3 (TNS3), phosphatase and tensin homologue (PTEN), and phosphoinositide-3-kinase (PI3K) in cell migration.
  • Analyzed phosphorylation events and complex rearrangements upon epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) stimulation.

Main Results:

  • Discovered a phosphorylation-mediated switch involving DLC1, TNS3, PTEN, and PI3K.
  • Demonstrated that growth factor stimulation triggers complex rearrangements, leading to TNS3-PI3K at the leading edge for Rac1 activation and PTEN-DLC1 at the posterior for RhoA activation.
  • Identified specific Thr residue phosphorylation on TNS3 and PTEN as critical for this switch.

Conclusions:

  • A core signaling mechanism couples external motility stimuli to the spatiotemporal activation of Rac1 and RhoA.
  • This mechanism precisely controls directional cell migration by orchestrating the localization and activity of signaling complexes.

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