IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules
Sara Bisi,
Stefano Marchesi,
Abrar Rizvi,
Davide Carra,
Galina V. Beznoussenko,
Ines Ferrara,
Gianluca Deflorian,
Alexander Mironov,
Giovanni Bertalot,
Federica Pisati,
Amanda Oldani,
Angela Cattaneo,
Ghazaleh Saberamoli,
Salvatore Pece,
Giuseppe Viale,
Angela Bachi,
Claudio Tripodo,
Giorgio Scita () and
Andrea Disanza
Additional contact information
Sara Bisi: IFOM, the FIRC Institute of Molecular Oncology
Stefano Marchesi: IFOM, the FIRC Institute of Molecular Oncology
Abrar Rizvi: IFOM, the FIRC Institute of Molecular Oncology
Davide Carra: IFOM, the FIRC Institute of Molecular Oncology
Galina V. Beznoussenko: IFOM, the FIRC Institute of Molecular Oncology
Ines Ferrara: University of Palermo School of Medicine
Gianluca Deflorian: Cogentech, S.R.L.
Alexander Mironov: IFOM, the FIRC Institute of Molecular Oncology
Giovanni Bertalot: European Institute of Oncology (IEO) IRCCS
Federica Pisati: Cogentech, S.R.L.
Amanda Oldani: IFOM, the FIRC Institute of Molecular Oncology
Angela Cattaneo: Cogentech, S.R.L.
Ghazaleh Saberamoli: IFOM, the FIRC Institute of Molecular Oncology
Salvatore Pece: European Institute of Oncology (IEO) IRCCS
Giuseppe Viale: European Institute of Oncology (IEO) IRCCS
Angela Bachi: IFOM, the FIRC Institute of Molecular Oncology
Claudio Tripodo: IFOM, the FIRC Institute of Molecular Oncology
Giorgio Scita: IFOM, the FIRC Institute of Molecular Oncology
Andrea Disanza: IFOM, the FIRC Institute of Molecular Oncology
Nature Communications, 2020, vol. 11, issue 1, 1-23
Abstract:
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.
Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17091-x
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DOI: 10.1038/s41467-020-17091-x
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