RT Journal Article
T1 The HERC1 ubiquitin ligase regulates presynaptic membrane dynamics of central synapses
T2 La ubiquitina ligasa HERC1 regula la dinámica de la membrana presináptica de las sinapsis centrales
A1 Montes-Fernández, Mª Ángeles
A1 Pérez-Villegas, E.
A1 García-Gonzalo, Francesc R.
A1 Pedrazza, Leonardo
A1 Rosa, José Luis
A1 Álvarez de Toledo, Guillermo
A1 Armengol Butrón de Mújica, José Ángel
K1 HERC1
K1 Ratón tambaleante
K1 Dinámica presináptica
K1 Autofagia
K1 Vesículas sinápticas
K1 Endosomas
K1 Autofagosomas
AB 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.
PB Nature Portfolio
YR 2020
FD 2020-07-21
LK https://hdl.handle.net/10433/25735
UL https://hdl.handle.net/10433/25735
LA en
NO Scientific RepoRtS (2020) 10:12057
NO Departamento fisiología, anatomía y biología celular
DS RIO
RD May 9, 2026