Hochapfel, Florian and Denk, Lucia and Mendl, Gudrun and Schulze, Ulf and Maassen, Christine and Zaytseva, Yulia and Pavenstaedt, Hermann and Weide, Thomas and Rachel, Reinhard and Witzgall, Ralph and Krahn, Michael P. (2017) Distinct functions of Crumbs regulating slit diaphragms and endocytosis in Drosophila nephrocytes. CELLULAR AND MOLECULAR LIFE SCIENCES, 74 (24). pp. 4573-4586. ISSN 1420-682X, 1420-9071
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MAMMALIAN EPITHELIAL-CELLS; ZONULA ADHERENS FORMATION; TIGHT JUNCTION PROTEIN; APICAL MEMBRANE; PHOTORECEPTOR MORPHOGENESIS; NEPHROTIC SYNDROME; APKC-LAMBDA/IOTA; POLARITY DEFECTS; COMPLEX; MOESIN; Nephrocyte; Podocyte; Crumbs; Moesin; Slit diaphragm; Endocytosis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 19 Feb 2019 07:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1815 |
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