Sphingomyelin clustering is essential for the formation of microvilli

Junichi Ikenouchi, Megumi Hirata, Shigenobu Yonemura, Masato Umeda

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


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 b (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.

Original languageEnglish
Pages (from-to)3585-3592
Number of pages8
JournalJournal of cell science
Issue number16
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Cell Biology


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