Dystrobrevin controls neurotransmitter release and muscle Ca 2+transients by localizing BK channels in Caenorhabditis elegans

Abstract

Dystrobrevin is a major component of a dystrophin-associated protein complex. It is widely expressed in mammalian tissues, including the nervous system, in which it is localized to the presynaptic nerve terminal with unknown function. In a genetic screen for suppressors of a lethargic phenotype caused by a gain-of-function isoform of SLO-1 in Caenorhabditis elegans, we isolated multiple loss-of-function (lf) mutants of the dystrobrevin gene dyb-1. dyb-1(lf) phenocopied slo-1(lf), causing increased neurotransmitter release at the neuromuscular junction, increased frequency of Ca 2+ transients in body-wall muscle, and abnormal locomotion behavior. Neuron- and musclespecific rescue experiments suggest that DYB-1 is required for SLO-1 function in both neurons and muscle cells. DYB-1 colocalized with SLO-1 at presynaptic sites in neurons and dense body regions in muscle cells, and dyb-1(lf) caused SLO-1 mislocalization in both types of cells without altering SLO-1 protein level. The neuronal phenotypes of dyb-1(lf) α-dystrobrevin-1. These observations revealed novel functions of the BK channel in regulating muscle Ca 2+ transients and of dystrobrevin in controlling neurotransmitter release and muscle Ca 2+ transients by localizing the BK channel. © 2011 the authors.