IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules.

It is unclear whether the establishment of apical–basal cell polarity during the generation of epithelial lumens requires molecules acting at the plasma membrane/actin interface. Here, we show that the I-BAR-containing IRSp53 protein controls lumen formation and the positioning of the polarity determinants aPKC and podocalyxin. Molecularly, IRSp53 acts by regulating the localization and activity of the small GTPase RAB35, and by interacting with the actin capping protein EPS8. Using correlative light and electron microscopy, we further show that IRSp53 ensures the shape and continuity of the opposing plasma membrane of two daughter cells, leading to the formation of a single apical lumen. Genetic removal of IRSp53 results in abnormal renal tubulogenesis, with altered tubular polarity and architectural organization. Thus, IRSp53 acts as a membrane curvature-sensing platform for the assembly of multi-protein complexes that control the trafficking of apical determinants and the integrity of the luminal plasma membrane. The I-BAR protein IRSp53 senses membrane curvature but its physiological role is unclear. Here, the authors show that during early lumen morphogenesis, IRSp53 controls the shape of the apical plasma membrane and polarized trafficking and ensures the correct epithelial tubular architecture and if deleted, affects renal tubules morphogenesis in various organisms. [ABSTRACT FROM AUTHOR]