FBS Colloquia No.240Laboratory of Single Molecule Biology

PTEN-PI(4,5)P2 positive feedback for stabilizing asymmetric PI(3,4,5)P3 pattern in migrating cell.

In order for a cell to move, it is necessary to form asymmetric signal in the cell. PI(3,4,5)P3, a phosphatidylinositol lipid, is well known as one of the major signaling molecules responsible for cell polarization. Since PI(3,4,5)P3 promotes the formation of pseudopods, the region where PI(3,4,5)P3 is localized become the “anterior” of the cells. Conversely, PTEN, a 3-phosphatase of PI(3,4,5)P3, acts on the “posterior” region for suppression of PI(3,4,5)P3 production. However, the mechanism for the membrane accumulation of PTEN hasremained to be clarified. Here, we developed an in vitro single-molecule imaging assay system to analyze the interaction between PTEN and lipids. Single-molecule imaging revealed that PTEN’s membrane binding is stabilized by its enzymatic product, PI(4,5)P2. PTEN-PI(4,5)P2 interaction enabled efficient cell migration through the PI(3,4,5)P3 distribution restricted to the anterior. These results demonstrate that a PI(4,5)P2-mediated positive feedback mechanism for the PTEN accumulation underlies the anterior-posterior polarization in motile cells.