Expression of coat proteins changes during postnatal development in selected areas of the rat brain

It is well known that clathrin-mediated endocytosis is crucial for the normal functioning and integrity of neurons in the central nervous system. In this study we attempted to correlate the expression of coat proteins with development in different areas of rat brain. By Western blot, we studied the expression of AP-2, GGA1 and GGA2 in striatum, cerebellum, brain stem, cerebral cortex and hippocampus of newborn rats and during post-natal development; 5, 15, 30, 60, 90 or 150 days after birth. We observed that the expression of the α2 subunit of AP-2 increased substantially between the 15th and 30th day after birth in all areas studied, excepting the cerebellum and cortex. On the other hand, the expression of the α1 subunit does not change significantly during the development in any of the areas under study. We also noted that the expression of the μ2 subunit did not follow the pattern of α2 during development. In general terms, the expression of GGA1 and GGA2 followed a similar pattern to that of AP-2, although these proteins increased significantly in the cerebral cortex from the 15th day after birth. Moreover, presenilin-1, a protein associated with aging and neurodegeneration, shows an expression pattern similar to coat proteins in the striatum and cortex. These results suggest that proteins that conform the intracellular transport machinery in the brain cells seems to accompany development, according to the maturation of the different brain areas. © 2012 ISDN.Fil: Borgonovo, Janina Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Capella, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Seltzer, Alicia Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

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

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.Fil: Borgonovo, Janina Edith. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; ArgentinaFil: Troncoso, Mariana Elizabeth. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Lucas, José J.. Universidad Autónoma de Madrid. Consejo superior de Investigaciones Científicas. Centro de Biología Molecular "Severo Ochoa"; EspañaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; Argentin