title: 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 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.
authors: Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
authors: Bojun
authors: B
authors: Chen
authors: Ping
authors: P
authors: Liu
authors: Haiying
authors: H
authors: Zhan
authors: Zhao-Wen
authors: ZW
authors: Wang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D049029:Dystrophin-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D017729:Presynaptic Terminals / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C479075:Dyb-1 protein, C elegans; D049029:Dystrophin-Associated Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009419:Nerve Tissue Proteins; C098885:dystrobrevin; C494845:slo-1 protein, C elegans; D002118:Calcium