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.

IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules / S. Bisi, S. Marchesi, A. Rizvi, D. Carra, G.V. Beznoussenko, I. Ferrara, G. Deflorian, A. Mironov, G. Bertalot, F. Pisati, A. Oldani, A. Cattaneo, G. Saberamoli, S. Pece, G. Viale, A. Bachi, C. Tripodo, G. Scita, A. Disanza. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 11:1(2020 Jul 14). [10.1038/s41467-020-17091-x]

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

S. Bisi
Primo
;
S. Marchesi
Secondo
;
F. Pisati;S. Pece;G. Viale;G. Scita
Penultimo
;
2020-07-14

Abstract

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.
Settore MED/04 - Patologia Generale
Settore MED/08 - Anatomia Patologica
Role of the YAP/TAZ transcriptional regulators in cancer chemoresistance
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/758342
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