title: 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 that are found 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 the sialomucin membrane protein podocalyxin-1 at microvilli. Podocalyxin-1 recruits ezrin/radixin/moesin (ERM)-binding phosphoprotein-50 (EBP50; also known as NHERF1), which recruits ERM proteins and phosphatidylinositol 4-phosphate 5-kinase β (PIP5Kβ). Thus, clustering of PIP5Kβ 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 the cytoskeletal proteins from which microvilli are formed, and it clarified the physiological importance of the chemical properties of sphingomyelin that facilitate cluster formation.
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan. ikenouchi@kyushu-u.org
authors.forename: Junichi
authors.initials: J
authors.lastname: Ikenouchi
authors.forename: Megumi
authors.initials: M
authors.lastname: Hirata
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Masato
authors.initials: M
authors.lastname: Umeda
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008871:Microvilli / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D012795:Sialoglycoproteins; D013109:Sphingomyelins; C001643:podocalyxin
keywords: Apical membrane; ERM; Epithelial polarity; Lysenin; Microvilli; Sphingomyelin