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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
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
Substances
-
Indicators and Reagents
-
Luminescent Proteins
-
Nucleotides, Cyclic
-
Phosphatidylinositol Phosphates
-
Phosphatidylinositols
-
Polymers
-
Tumor Suppressor Proteins
-
phosphatidylinositol 3,4,5-triphosphate
-
Green Fluorescent Proteins
-
Phosphoric Monoester Hydrolases
-
PTEN Phosphohydrolase