TORC2 and chemotaxis in Dictyostelium discoideum

Yoichiro Kamimura, Huaqing Cai, Peter N. Devreotes

Research output: Contribution to journalArticle

Abstract

Chemotaxis involves the cellular reactions of motility and directional sensing, which enable cells to sense and move along extracellular chemical gradients. Dictyostelium discoideum cells display robust chemotactic responses to cAMP. Extensive characterization of these responses has provided insights into the mechanisms of chemotaxis. In this system, chemotaxis is composed of multiple signaling pathways including the TORC2- PDK-PKB module where target of rapamycin complex 2 (TORC2) and phosphoinositide-dependent kinase (PDK) function as upstream activators of protein kinase B (PKBs) through hydrophobic motif (HM) and activation loop (AL) phosphorylations, respectively. This module forms a unique signaling pathway where chemoattractant signals are separated and then converge on substrate phosphorylations mediated by two PKB homologues, phosphatidylinositol (3,4,5)-tris phosphate (PtdIns (3,4,5)P3)-dependent PKBA and -independent PKBR1. PKBA and PKBR1 contribute minor, redundant and major activities, respectively. Consistently, pkbR1 cells are more severely impaired in chemotaxis than cells lacking PKBA or PtdIns (3,4,5)P3. The TORC2-PDK-PKB module is selectively activated at the front of morphologically polarized cells by an upstream regulator, RasC, during chemotaxis. Spatial dysregulation of this pathway, exemplified by pten cells or cells expressing an active form of RasC where PtdIns (3,4,5) P3-PKBAor TORC2-dependent PKBR1 is overactivated, respectively, leads to extension of pseudopods all around cells and to severe chemotaxis defects. These results strongly suggest that this pathway has critical roles in linking chemotactic stimuli to cytoskeletal rearrangements. These studies shed light on the function and regulation of the TORC2-PDK-PKB pathway from a new perspective.

Original languageEnglish (US)
Pages (from-to)125-142
Number of pages18
JournalEnzymes
Volume28
Issue numberC
DOIs
StatePublished - Oct 5 2010

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Biochemistry
  • Molecular Biology

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