Phosphatidylinositol 4, 5 bisphosphate and the actin cytoskeleton

Dynamic changes in PM PIP2 have been implicated in the regulation of many processes that are dependent on actin polymerization and remodeling. PIP2 is synthesized primarily by the type I phosphatidylinositol 4 phosphate 5 kinases (PIP5Ks), and there are three major isoforms, called α, β and γ. There is emerging evidence that these PIP5Ks have unique as well as overlapping functions. This review will focus on the isoform-specific roles of individual PIP5K as they relate to the regulation of the actin cytoskeleton. We will review recent advances that establish PIP2 as a critical regulator of actin polymerization and cytoskeleton/membrane linkages, and show how binding of cytoskeletal proteins to membrane PIP2 might alter lateral or transverse movement of lipids to affect raft formation or lipid asymmetry. The mechanisms for specifying localized increase in PIP2 to regulate dynamic actin remodeling will also be discussed.