Related Experiment Video

Updated: Jun 12, 2026

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 Ras signaling complex controls the RasC-TORC2 pathway and directed cell migration

Pascale G Charest1, Zhouxin Shen, Ashley Lakoduk

  • 1Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0380, USA.

Developmental Cell
|May 25, 2010
PubMed

Insights

We discovered a Ras signaling complex that controls cell movement (chemotaxis) in Dictyostelium. This complex regulates RasC activity and downstream pathways at the cell

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Ras signaling pathways are crucial for regulating cell behavior, including chemotaxis.
  • The precise mechanisms controlling Ras activity spatiotemporally during chemotaxis are not fully understood.
  • Understanding these mechanisms is key to deciphering cellular responses to external stimuli.

Purpose of the Study:

  • To elucidate the molecular mechanisms controlling Ras activity during Dictyostelium chemotaxis.
  • To identify the components of the Ras signaling complex involved in chemotaxis.
  • To investigate the role of this complex in regulating F-actin dynamics and signal relay.

Main Methods:

  • Identification and characterization of a novel Ras signaling complex.
  • Biochemical assays to determine protein interactions and complex assembly.
  • Microscopy techniques to visualize complex localization and dynamics in chemotaxing cells.

Main Results:

  • Discovered a Ras signaling complex comprising Aimless (RasGEF), RasGEFH, PP2A, and Sca1.
  • Demonstrated recruitment of the Sca1/RasGEF/PP2A complex to the leading edge of chemotaxing cells.
  • Showed that this complex controls RasC activation, F-actin dynamics, and TORC2-Akt/PKB pathway activation.
  • Identified a negative feedback loop where PKB phosphorylates Sca1, regulating complex localization and RasC activity.

Conclusions:

  • Uncovered a molecular mechanism for spatiotemporal control of RasC activity at the leading edge.
  • Established the role of the Sca1/RasGEF/PP2A complex in regulating chemotaxis and signal transduction.
  • Provided insights into the intricate regulation of the TORC2-Akt/PKB pathway during directed cell migration.

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