TORC2 and chemotaxis in Dictyostelium discoideum

Yoichiro Kamimura, Huaqing Cai, Peter N Devreotes

Research output: Book/ReportBook

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)
PublisherUnknown Publisher
Number of pages18
Volume28
EditionC
DOIs
StatePublished - 2010

Publication series

NameEnzymes
No.C
Volume28
ISSN (Print)18746047

Fingerprint

Proto-Oncogene Proteins c-akt
Dictyostelium
Chemotaxis
Phosphatidylinositols
1-Phosphatidylinositol 4-Kinase
Phosphorylation
Chemotactic Factors
Phosphotransferases
Pseudopodia
Chemical activation
Critical Pathways
Phosphates
Cells
TOR complex 2
Defects
Substrates
Signal Transduction
phosphatidylinositol 3,4,5-triphosphate

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Biophysics
  • Molecular Biology

Cite this

Kamimura, Y., Cai, H., & Devreotes, P. N. (2010). TORC2 and chemotaxis in Dictyostelium discoideum. (C ed.) (Enzymes; Vol. 28, No. C). Unknown Publisher. https://doi.org/10.1016/S1874-6047(10)28006-X

TORC2 and chemotaxis in Dictyostelium discoideum. / Kamimura, Yoichiro; Cai, Huaqing; Devreotes, Peter N.

C ed. Unknown Publisher, 2010. 18 p. (Enzymes; Vol. 28, No. C).

Research output: Book/ReportBook

Kamimura, Y, Cai, H & Devreotes, PN 2010, TORC2 and chemotaxis in Dictyostelium discoideum. Enzymes, no. C, vol. 28, vol. 28, C edn, Unknown Publisher. https://doi.org/10.1016/S1874-6047(10)28006-X
Kamimura Y, Cai H, Devreotes PN. TORC2 and chemotaxis in Dictyostelium discoideum. C ed. Unknown Publisher, 2010. 18 p. (Enzymes; C). https://doi.org/10.1016/S1874-6047(10)28006-X
Kamimura, Yoichiro ; Cai, Huaqing ; Devreotes, Peter N. / TORC2 and chemotaxis in Dictyostelium discoideum. C ed. Unknown Publisher, 2010. 18 p. (Enzymes; C).
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