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Updated: Jun 10, 2026

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
09:40

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

Ras-mediated activation of the TORC2-PKB pathway is critical for chemotaxis

Huaqing Cai1, Satarupa Das, Yoichiro Kamimura

  • 1Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.

The Journal of Cell Biology
|July 28, 2010
PubMed

Insights

Ras proteins regulate cell migration by controlling TORC2 signaling. This study reveals RasC activates TORC2, impacting cell movement and cytoskeleton dynamics in Dictyostelium discoideum.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • G protein-coupled receptors activate Ras proteins in chemotactic cells, but the link to cell migration is not fully understood.
  • Understanding how Ras-associated pathways influence cell motility is crucial for deciphering cellular responses to extracellular signals.

Purpose of the Study:

  • To elucidate the role of RasC in regulating TORC2 (target of rapamycin complex 2) signaling.
  • To investigate how RasC-mediated signaling affects cell migration and cytoskeletal dynamics in Dictyostelium discoideum.

Main Methods:

  • Investigated the effects of activated RasC on TORC2-mediated protein kinase B (PKB) activation and substrate phosphorylation.
  • Utilized genetic manipulation (PiaA deletion) and biochemical assays (immunocomplex analysis, inhibitor treatment) to probe the RasC-TORC2 interaction.
  • Observed changes in adenylyl cyclase activation, actin polymerization, pseudopodial activity, and chemotaxis kinetics.

Main Results:

  • Activated RasC prolongs TORC2-mediated PKB activation and substrate phosphorylation independently of phosphatidylinositol-(3,4,5)-trisphosphate.
  • RasC influences the kinetics of chemoattractant-induced adenylyl cyclase activation and actin polymerization, leading to impaired chemotaxis.
  • TORC2 subunit PiaA is essential for RasC's effects, and TORC2 directly binds to activated RasC.

Conclusions:

  • RasC acts as an upstream regulator of TORC2 signaling.
  • The TORC2-PKB pathway mediates the effects of activated Ras proteins on the cytoskeleton and cell migration.
  • This study establishes a novel link between Ras signaling and TORC2 in controlling cell motility.

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