2026-04-17T06:47:00Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1734982025-12-05T09:32:13Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917
RECERCAT author Montes Fernández, Mª Angeles author Pérez Villegas, Eva María author Garcia Gonzalo, Francesc author Pedrazza, Leonardo author Rosa López, José Luis author Alvarez de Toledo, Guillermo author Armengol, José Ángel 2021-01-28T13:57:57Z2021-01-28T13:57:57Z2020-07-212021-01-25T08:10:01Z HERC1 is a ubiquitin ligase protein, which, when mutated, induces several malformations and intellectual disability in humans. The animal model of HERC1 mutation is the mouse tambaleante characterized by: (1) overproduction of the protein; (2) cerebellar Purkinje cells death by autophagy; (3) dysregulation of autophagy in spinal cord motor neurons, and CA3 and neocortical pyramidal neurons; (4) impairment of associative learning, linked to altered spinogenesis and absence of LTP in the lateral amygdala; and, (5) motor impairment due to delayed action potential transmission, decrease synaptic transmission efficiency and altered myelination in the peripheral nervous system. To investigate the putative role of HERC1 in the presynaptic dynamics we have performed a series of experiments in cultured tambaleante hippocampal neurons by using transmission electron microscopy, FM1-43 destaining and immunocytochemistry. Our results show: (1) a decrease in the number of synaptic vesicles; (2) reduced active zones; (3) less clathrin immunoreactivity and less presynaptic endings over the hippocampal main dendritic trees; which contrast with (4) a greater number of endosomes and autophagosomes in the presynaptic endings of the tambaleante neurons relative to control ones. Altogether these results show an important role of HERC1 in the regulation of presynaptic membrane dynamics. cc by (c) Montes Fernández et al., 2020 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Ubiqüitina Autofàgia Malalties neurodegeneratives Ubiquitin Autophagy Neurodegenerative Diseases The HERC1 ubiquitin ligase regulates presynaptic membrane dynamics of central synapses info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion