RT info:eu-repo/semantics/article
T1 Moesin Regulates the Trafficking of Nascent Clathrin-coated Vesicles.
A1 Valenzuela Fernández, Agustín
A1 Barroso Gonza´lez, Jonathan
A1 Machado, José-David
A1 García Expósito, Laura
A2 Medicina Física y Farmacología
A2 Grupo "Inmunología Celular y Viral".
AB Clathrin-coated vesicles are responsible for the trafficking ofseveral internalized biological cargos. We have observed that theendogenous F-actin-linker moesin co-distributes with constitutivecomponents of clathrin-coated structures.Totalinternal reflectionfluorescence microscopy studies have shown that short interference RNA of moesin enhances the lateral movement of clathrincoated structures and provokes their abnormal clustering. Theaggregation of clathrin-coated structures has also been observedincells overexpressing N-moesin, a dominant-negative constructunable to bind to F-actin. Only overexpressed moesin constructswith an intact phosphatidylinositol 4,5-bisphosphate-bindingdomain co-distribute with clathrin-coated structures. Hence, thisN-terminal domain is mostly responsible for moesin/clathrincoated structure association. Biochemical endosome fractioningtogether with total internal reflection fluorescence microscopycomparative studies, between intact cells and plasma-membranesheets, 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 receptorrecycling defect that reduces cell-surface expression of the transferrin receptorandincreases theamount of sequestered transferrinligand. 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 clathrincoated vesicle-associated phosphatidylinositol 4,5-bisphosphateand actin cytoskeleton. Hence, functional alterations of moesinmay be involved in pathological disorders associated with clathrinmediated internalization or receptor recycling.
YR 2008
FD 2008
LK http://riull.ull.es/xmlui/handle/915/35375
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DS Repositorio institucional de la Universidad de La Laguna
RD 17-jun-2024