Moving PIP 3 About

Abstract

STKE Phosphatidylinositol-(3,4,5)-phosphate (PIP3), the product of phosphatidylinositol 3-kinase (PI3K), is important in the establishment of cell polarity. Horiguchi et al. provide evidence that PIP3 is produced not only at the plasma membrane by local activation of PI3K, but also at internal membranes that are then transported as PIP3-containing vesicles on microtubules to the growing tips of neuronal projections. First, they determined that GAKIN (guanylate kinase-associated kinesin) interacted with PIP3 binding protein (PIP3 BP); in vitro, GAKIN and PIP3 BP mediated the movement of PIP3 liposomes on microtubules. In PC12 cells and in cultured hippocampal neurons, tagged GAKIN, tagged PIP3 BP, and a marker for PIP3 were colocalized at the tips of neurites, and in hippocampal cells, these three molecules were most abundant in the longest neurite, the axon. Overexpression of a dominant-negative form of GAKIN (with the kinesin motor domain deleted) in PC12 cells decreased the abundance of PIP3 at neurite tips. In hippocampal neurons, overexpression of wild-type GAKIN or dominant-negative GAKIN disrupted the formation of the morphologically distinct axon-dendrite structure and produced cells with multiple, highly branched neurites. The authors suggest that PIP3 produced at internal membranes or PIP3 produced at the cell body may contribute to cell polarity. — NRG J. Cell Biol. 174 , 425 (2006).