Sphingomyelin clustering is essential for the formation of microvilli

Abstract

Cellular architectures require regulated mechanisms to correctly localize the appropriate plasma membrane lipids and proteins. Microvilli are dynamic, filamentous-actin based protrusions of the plasma membrane in the apical membrane of epithelial cells. However, it remains poorly understood how their formation is regulated. In the present study, we found that sphingomyelin clustering underlies the formation of microvilli. Clustering of sphingomyelin is required for the co-clustering of a sialomucin membrane protein podocalyxin-1 at microvilli. Podocalyxin-1 recruits ERM-binding phosphoprotein-50 (also known as NHERF1), which recruits Ezrin/Radixin/Moesin proteins (ERM) and phosphatidylinositol 4-phosphate 5-kinase beta (PIP5Kbeta). Thus, clustering of PIP5Kbeta leads to local accumulation of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2], which enhances the accumulation of ERM family proteins and induces the formation of microvilli. The present study revealed novel interactions between sphingomyelin and cytoskeletal proteins by which microvilli are formed, and it clarified the physiological importance of the chemical properties of sphingomyelin that facilitate cluster formation.