PI(4,5)P2 Clustering and Its Impact on Biological Functions

Located at the inner leaflet of the plasma membrane (PM), phosphatidylinositol 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 Ca2+ and Mg2+ 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.

Automated summary

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) is a crucial component located at the inner leaflet of the cell membrane, constituting only 1-2% of total membrane lipids. Its synthesis and turnover are spatially and temporally regulated. Various factors, such as multivalent cations and cellular proteins interacting with PI(4,5)P-2, contribute to its versatile and dynamic distribution within membranes.