RRC ID 29040
Author Iijima M, Devreotes P.
Title Tumor suppressor PTEN mediates sensing of chemoattractant gradients.
Journal Cell
Abstract Shallow gradients of chemoattractants, sensed by G protein-linked signaling pathways, elicit localized binding of PH domains specific for PI(3,4,5)P3 at sites on the membrane where rearrangements of the cytoskeleton and pseudopod extension occur. Disruption of the PI 3-phosphatase, PTEN, in Dictyostelium discoideum dramatically prolonged and broadened the PH domain relocation and actin polymerization responses, causing the cells lacking PTEN to follow a circuitous route toward the attractant. Exogenously expressed PTEN-GFP localized to the surface membrane at the rear of the cell. Membrane localization required a putative PI(4,5)P2 binding motif and was required for chemotaxis. These results suggest that specific phosphoinositides direct actin polymerization to the cell's leading edge and regulation of PTEN through a feedback loop plays a critical role in gradient sensing and directional migration.
Volume 109(5)
Pages 599-610
Published 2002-5-31
PII S0092867402007456
PMID 12062103
MeSH Actin Cytoskeleton / metabolism* Animals Cell Membrane / metabolism* Cell Polarity / physiology Chemotaxis / physiology* Cytosol / metabolism Dictyostelium / cytology Dictyostelium / enzymology* Dictyostelium / genetics Down-Regulation / physiology Green Fluorescent Proteins Indicators and Reagents / metabolism Luminescent Proteins / metabolism Mutation / genetics Nucleotides, Cyclic / genetics Nucleotides, Cyclic / metabolism PTEN Phosphohydrolase Phosphatidylinositol Phosphates / metabolism* Phosphatidylinositols / metabolism Phosphoric Monoester Hydrolases / deficiency* Phosphoric Monoester Hydrolases / genetics Polymers / metabolism Protein Structure, Tertiary / physiology Pseudopodia / metabolism* Pseudopodia / ultrastructure Tumor Suppressor Proteins / deficiency* Tumor Suppressor Proteins / genetics
IF 36.216
Times Cited 451
Cellular slime molds S00005