Endocytosis mediated by an atypical CUBAM complex modulates slit diaphragm dynamics in nephrocytes
| Autor: | Alexandra Atienza-Manuel, Joaquim Culi, Mar Ruiz-Gómez, Vicente Castillo-Mancho, Stefano De Renzis |
|---|---|
| Přispěvatelé: | Ministerio de Economía, Industria y Competitividad (España), Ministerio de Ciencia e Innovación (España), European Molecular Biology Laboratory, Fundación Ramón Areces |
| Rok vydání: | 2021 |
| Předmět: |
Diaphragm
Endocytic cycle Nephrocyte Receptors Cell Surface Biology Endocytosis Exocytosis Kidney Tubules Proximal Morphogenesis Cubam Animals Drosophila Proteins Slit diaphragm Molecular Biology rab5 GTP-Binding Proteins Podocytes Amnionless Cubilin LRP2 Cell biology Low Density Lipoprotein Receptor-Related Protein-2 Drosophila melanogaster Intercellular Junctions Multiprotein Complexes Drosophila Research Article Developmental Biology CUBAM endocytic receptor |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Development (Cambridge, England) article-version (VoR) Version of Record |
| Popis: | The vertebrate endocytic receptor CUBAM, consisting of three cubilin monomers complexed with a single amnionless molecule, plays a major role in protein reabsorption in the renal proximal tubule. Here, we show that Drosophila CUBAM is a tripartite complex composed of Amnionless and two cubilin paralogues, Cubilin and Cubilin2, and that it is required for nephrocyte slit diaphragm (SD) dynamics. Loss of CUBAM-mediated endocytosis induces dramatic morphological changes in nephrocytes and promotes enlarged ingressions of the external membrane and SD mislocalisation. These phenotypes result in part from an imbalance between endocytosis, which is strongly impaired in CUBAM mutants, and exocytosis in these highly active cells. Of note, rescuing receptor-mediated endocytosis by Megalin/LRP2 or Rab5 expression only partially restores SD positioning in CUBAM mutants, suggesting a specific requirement of CUBAM in SD degradation and/or recycling. This finding and the reported expression of CUBAM in podocytes suggest a possible unexpected conserved role for this endocytic receptor in vertebrate SD remodelling. Summary: A genetic study revealing that endocytosis mediated by an atypical CUBAM endocytic receptor, composed of Amnionless and two Cubilin paralogues, regulates slit diaphragm remodelling in Drosophila nephrocytes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|