Abstract
Phosphorylated forms of phosphatidylinositol are called phosphoinositides and play important roles in lipid signaling, cell signaling, and membrane trafficking. Cytoskeletal proteins were the first proteins shown to be regulated by polyphosphoinositides (PPIs). This chapter focuses on recent advances showing how PPIs are involved in the regulation of actin polymerization and the formation of cytoskeleton/membrane links, and how binding of cytoskeletal proteins to membrane PPIs may relate to the lateral or transverse movement of lipids to affect raft formation or lipid asymmetry. It begins with an account of stimulating site-specific actin polymerization in cells, and thereafter discusses the mechanisms of actin polymerization. Under this, it suggests that site-specific actin polymerization in vivo occurs primarily at the rapidly growing end (+) of actin nuclei. Transient PIP5K overexpression has many effects. These include many actin-dependent processes, such as N-WASP-dependent actin comet tail formation, Rho and Rho-kinase dependent actin stress fiber formation, N-cadherin-mediated cell adhesion, Arf6-regulated plasma membrane-endosome recycling, neurite remodeling, and phagocytosis. Specific functional regulation by PIP2 has now been confirmed for multiple proteins, and manipulation of PIP2 levels in cells consistently shows large effects on the actin-base cytoskeleton that are consistent with many observations from in vitro biochemical studies. A challenge for future studies is to delineate more clearly the localization and diffusivity of PIP2 in the different membranes within the cell, and to evaluate how the large number of PIP2 ligands is selectively regulated when changes in PIP2 levels or localization are generated in vivo.
Original language | English (US) |
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Title of host publication | Handbook of Cell Signaling, Second Edition |
Publisher | Elsevier |
Pages | 1141-1150 |
Number of pages | 10 |
Volume | 2 |
ISBN (Electronic) | 9780123741455 |
DOIs | |
State | Published - Jan 1 2009 |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology