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R-Ras controls membrane protrusion and cell migration through the spatial regulation of Rac and Rho

Michele A Wozniak1, Lina Kwong, David Chodniewicz

  • 1Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA.

Molecular Biology of the Cell
|November 5, 2004
PubMed

Insights

Ras-related C3 botulinum toxin substrate (R-Ras) regulates cell migration by controlling Rac and Rho GTPase activity. R-Ras is crucial for cell movement, mediating a switch in GTPase activity at the leading edge.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Spatial coordination of Rac and Rho GTPase activity is vital for cell migration.
  • The precise molecular mechanisms governing these GTPases during migration remain unclear.

Purpose of the Study:

  • To elucidate the role of R-Ras in regulating cell migration.
  • To investigate how R-Ras influences Rac and Rho GTPase activity spatially during cell movement.

Main Methods:

  • Utilized constitutively activated and dominant-negative R-Ras mutants.
  • Employed small interfering RNA (siRNA) to deplete endogenous R-Ras.
  • Assessed cell migration, membrane protrusion, and GTPase activity.
  • Investigated the involvement of PI3-Kinase signaling.

Main Results:

  • Constitutively activated R-Ras inhibited membrane protrusion and random migration.
  • Dominant-negative R-Ras enhanced migrational persistence and protrusion.
  • R-Ras depletion via siRNA abolished cell migration.
  • R-Ras modulated Rac and Rho activity, decreasing Rac and increasing Rho, or vice versa.
  • Endogenous R-Ras localized and was activated at the leading edge upon adhesion.
  • R-Ras effects on migration were PI3-Kinase dependent.

Conclusions:

  • R-Ras is essential for cell migration.
  • R-Ras spatially regulates the switch between Rac and Rho activity at the leading edge.
  • R-Ras acts through PI3-Kinase to control cell migration dynamics.

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