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Artículo

Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes

Borgonovo, Janina EdithIcon ; Troncoso, Mariana ElizabethIcon ; Lucas, José J.; Sosa Escudero, Miguel AngelIcon
Fecha de publicación: 03/2013
Editorial: Elsevier
Revista: Experimental Neurology
ISSN: 0014-4886
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Neurociencias

Resumen

Clathrin-mediated endocytosis plays an important role in the maintenance of neuronal integrity in the synaptic terminals. Here we studied the effect of anomalous polyglutamine expansion in huntingtin on the interaction of coat proteins with membranes, in areas of mouse brain or in cultured striatal cells. We observed that this anomaly induces a redistribution of AP-2, but not other coat proteins, from the membrane to the cytosol in the striatum, and in the cultured striatal cells. It was also noted that huntingtin associates with AP-2, and that this association decreases due to the mutation in huntingtin. This decreased receptor-mediated endocytosis, measured by the internalization of transferrin in the mutated cells. It was also confirmed that huntingtin mutation made the cells more vulnerable to the action of quinolinic acid, with an increasing degradation of the AP-2 alpha subunits. On the basis of these results, we conclude that abnormal polyglutamine expansion in huntingtin affects clathrin-mediated endocytosis, and may be one of the pathogenic mechanisms of neurodegeneration.
Palabras clave: Endocytosis , Clathrin Coated Vesicles , Neurodegeneration , Huntingtin , Huntington'S Disease
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/10077
URL: http://www.sciencedirect.com/science/article/pii/S0014488612004426
DOI: http://dx.doi.org/10.1016/j.expneurol.2012.11.025
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Articulos(IHEM)
Articulos de INST. HISTOLOGIA Y EMBRIOLOGIA DE MEND DR.M.BURGOS
Citación
Borgonovo, Janina Edith; Troncoso, Mariana Elizabeth; Lucas, José J.; Sosa Escudero, Miguel Angel; Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes; Elsevier; Experimental Neurology; 241; 3-2013; 75-83
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