Dystrobrevin Controls Neurotransmitter Release and Muscle Ca2+Transients by Localizing BK Channels inCaenorhabditis elegans
Year: 2011
Type: article
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 muscle-specific 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) were partially rescued by mouse 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.
Source: Journal of Neuroscience
Authors: Bojun Chen, Ping Liu, Haiying Zhan, Zhao-Wen Wang
Institution: UConn Health
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W2066514175