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1: Cell. 2002 May 31;109(5):599-610.
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Comment in:
Tumor suppressor PTEN mediates sensing of chemoattractant gradients.

Iijima M, Devreotes P.

Department of Cell Biology, Johns Hopkins University, School of Medicine, 21205, Baltimore, MD, USA

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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PMID: 12062103 [PubMed - indexed for MEDLINE]