TY - JOUR
T1 - Tumor suppressor PTEN mediates sensing of chemoattractant gradients
AU - Iijima, Miho
AU - Devreotes, Peter
N1 - Funding Information:
This work was supported by NIH grants GM34933 and 57874 to P.N.D. The authors wish to thank Linnan Tang for constructing the Supplemental Video S7 and Chris Janetopoulos for assistance in fluorescence microscopy.
PY - 2002/5/31
Y1 - 2002/5/31
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(02)00745-6
DO - 10.1016/S0092-8674(02)00745-6
M3 - Article
C2 - 12062103
AN - SCOPUS:0037205230
SN - 0092-8674
VL - 109
SP - 599
EP - 610
JO - Cell
JF - Cell
IS - 5
ER -