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

J Neurosci. 2011 Nov 30;31(48):17338-47. doi: 10.1523/JNEUROSCI.3638-11.2011.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Calcium / metabolism*
  • Dystrophin-Associated Proteins / genetics
  • Dystrophin-Associated Proteins / metabolism*
  • Large-Conductance Calcium-Activated Potassium Channels / genetics
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Muscle Fibers, Skeletal
  • Muscle, Skeletal / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / metabolism*
  • Neurons / metabolism
  • Phenotype
  • Presynaptic Terminals / metabolism
  • Synaptic Transmission / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Dyb-1 protein, C elegans
  • Dystrophin-Associated Proteins
  • Large-Conductance Calcium-Activated Potassium Channels
  • Nerve Tissue Proteins
  • dystrobrevin
  • slo-1 protein, C elegans
  • Calcium