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. 2002 May 31;109(5):599-610.
doi: 10.1016/s0092-8674(02)00745-6.

Tumor suppressor PTEN mediates sensing of chemoattractant gradients

Miho Iijima  1 , Peter Devreotes
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Free article

Tumor suppressor PTEN mediates sensing of chemoattractant gradients

Miho Iijima et al. Cell. .
Free article

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.

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