Moesin Regulates the Trafficking of Nascent Clathrin-coated Vesicles
| Autor: | Laura García-Expósito, Jonathan Barroso-González, Agustín Valenzuela-Fernández, José-David Machado |
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| Rok vydání: | 2009 |
| Předmět: |
Receptor recycling
biology Endosome Vesicle Moesin Microfilament Proteins Endocytic cycle Transferrin Clathrin-Coated Vesicles Transferrin receptor macromolecular substances Cell Biology Actin cytoskeleton Biochemistry Clathrin Cell biology Protein Transport Receptors Transferrin biology.protein Humans RNA Small Interfering Molecular Biology HeLa Cells Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 284:2419-2434 |
| ISSN: | 0021-9258 |
| Popis: | Clathrin-coated vesicles are responsible for the trafficking of several internalized biological cargos. We have observed that the endogenous F-actin-linker moesin co-distributes with constitutive components of clathrin-coated structures. Total internal reflection fluorescence microscopy studies have shown that short interference RNA of moesin enhances the lateral movement of clathrin-coated structures and provokes their abnormal clustering. The aggregation of clathrin-coated structures has also been observed in cells overexpressing N-moesin, a dominant-negative construct unable to bind to F-actin. Only overexpressed moesin constructs with an intact phosphatidylinositol 4,5-bisphosphate-binding domain co-distribute with clathrin-coated structures. Hence, this N-terminal domain is mostly responsible for moesin/clathrin-coated structure association. Biochemical endosome fractioning together with total internal reflection fluorescence microscopy comparative studies, between intact cells and plasma-membrane sheets, indicate that moesin knockdown provokes the accumulation of endocytic rab5-clathrin-coated vesicles carrying the transferrin receptor. The altered trafficking of these endocytic rab5-clathrin-coated vesicles accounts for a transferrin receptor recycling defect that reduces cell-surface expression of the transferrin receptor and increases the amount of sequestered transferrin ligand. Therefore, we propose that moesin is a clathrin-coated vesicle linker that drives cargo trafficking and acts on nascent rab5-clathrin-coated vesicles by simultaneously binding to clathrin-coated vesicle-associated phosphatidylinositol 4,5-bisphosphate and actin cytoskeleton. Hence, functional alterations of moesin may be involved in pathological disorders associated with clathrin-mediated internalization or receptor recycling. |
| Databáze: | OpenAIRE |
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