PI(4,5)P<sub>2</sub> Clustering and Its Impact on Biological Functions
Yi Wen, Volker M. Vogt, Gerald W. Feigenson
Abstract
Located at the inner leaflet of the plasma membrane (PM), phosphatidyl-inositol 4,5-bisphosphate [PI(4,5)P 2 ] composes only 1–2 mol% of total PM lipids. With its synthesis and turnover both spatially and temporally regulated, PI(4,5)P 2 recruits and interacts with hundreds of cellular proteins to support a broad spectrum of cellular functions. Several factors contribute to the versatile and dynamic distribution of PI(4,5)P 2 in membranes. Physiological multivalent cations such as Ca 2+ and Mg 2+ can bridge between PI(4,5)P 2 headgroups, forming nanoscopic PI(4,5)P 2 –cation clusters. The distinct lipid environment surrounding PI(4,5)P 2 affects the degree of PI(4,5)P 2 clustering. In addition, diverse cellular proteins interacting with PI(4,5)P 2 can further regulate PI(4,5)P 2 lateral distribution and accessibility. This review summarizes the current understanding of PI(4,5)P 2 behavior in both cells and model membranes, with emphasis on both multivalent cation– and protein-induced PI(4,5)P 2 clustering. Understanding the nature of spatially separated pools of PI(4,5)P 2 is fundamental to cell biology.