The HERC1 ubiquitin ligase regulates presynaptic membrane dynamics of central synapses.

Scientific Reports
Mª Angeles Montes-FernándezJosé A Armengol

Abstract

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 neu...Continue Reading

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Citations

Dec 18, 2020·Frontiers in Neuroanatomy·Eva M Pérez-VillegasJosé A Armengol

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Methods Mentioned

BETA
GTPases
pull-down
GTPase
genotyping
pull-downs
electrophoresis

Software Mentioned

TILL Vision
SYT
Igor Pro
Photoshop
ImageJ

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