A mutation in Ca_V2.1 linked to a severe neurodevelopmental disorder impairs channel gating.

ABSTRACT: Ca²⁺ flux into axon terminals via P-/Q-type Ca_V2.1 channels is the trigger for neurotransmitter vesicle release at neuromuscular junctions (NMJs) and many central synapses. Recently, an arginine to proline substitution (R1673P) in the S4 voltage-sensing helix of the fourth membrane-bound repeat of Ca_V2.1 was linked to a severe neurological disorder characterized by generalized hypotonia, ataxia, cerebellar atrophy, and global developmental delay. The R1673P mutation was proposed to cause a gain of function in Ca_V2.1 leading to neuronal Ca²⁺ toxicity based on the ability of the mutant channel to rescue the photoreceptor response in Ca_V2.1-deficient Drosophila cacophony larvae. Here, we show that the corresponding mutat

SUBMITTER: Tyagi S 

PROVIDER: S-EPMC6571999 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature