RRC ID 48901
Author Hochapfel F, Denk L, Mendl G, Schulze U, Maaßen C, Zaytseva Y, Pavenstädt H, Weide T, Rachel R, Witzgall R, Krahn MP.
Title Distinct functions of Crumbs regulating slit diaphragms and endocytosis in Drosophila nephrocytes.
Journal Cell Mol Life Sci
Abstract Mammalian podocytes, the key determinants of the kidney's filtration barrier, differentiate from columnar epithelial cells and several key determinants of apical-basal polarity in the conventional epithelia have been shown to regulate podocyte morphogenesis and function. However, little is known about the role of Crumbs, a conserved polarity regulator in many epithelia, for slit-diaphragm formation and podocyte function. In this study, we used Drosophila nephrocytes as model system for mammalian podocytes and identified a conserved function of Crumbs proteins for cellular morphogenesis, nephrocyte diaphragm assembly/maintenance, and endocytosis. Nephrocyte-specific knock-down of Crumbs results in disturbed nephrocyte diaphragm assembly/maintenance and decreased endocytosis, which can be rescued by Drosophila Crumbs as well as human Crumbs2 and Crumbs3, which were both expressed in human podocytes. In contrast to the extracellular domain, which facilitates nephrocyte diaphragm assembly/maintenance, the intracellular FERM-interaction motif of Crumbs is essential for regulating endocytosis. Moreover, Moesin, which binds to the FERM-binding domain of Crumbs, is essential for efficient endocytosis. Thus, we describe here a new mechanism of nephrocyte development and function, which is likely to be conserved in mammalian podocytes.
Volume 74(24)
Pages 4573-4586
Published 2017-12-1
DOI 10.1007/s00018-017-2593-y
PII 10.1007/s00018-017-2593-y
PMID 28717874
MeSH Animals Diaphragm / metabolism Diaphragm / physiology* Drosophila / metabolism* Drosophila / physiology* Drosophila Proteins / metabolism* Endocytosis / physiology* Epithelial Cells / metabolism Humans Mammals / metabolism Membrane Proteins / metabolism* Microfilament Proteins / metabolism Podocytes / metabolism
IF 6.496
Times Cited 8
Drosophila 15342R-2 12021R-4