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Updated: Jun 12, 2026
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
Summary
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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