title: A novel auxiliary subunit critical to BK channel function in Caenorhabditis elegans.
abstract: The BK channel is a Ca²+- and voltage-gated potassium channel with many important physiological functions. To identify proteins important to its function in vivo, we screened for Caenorhabditis elegans mutants that suppressed a lethargic phenotype caused by expressing a gain-of-function (gf) isoform of the BK channel α-subunit SLO-1. BKIP-1 (for BK channel interacting protein), a small peptide with no significant homology to any previously characterized molecules, was thus identified. BKIP-1 and SLO-1 showed similar expression and subcellular localization patterns and appeared to interact physically through discrete domains. bkip-1 loss-of-function (lf) mutants phenocopied slo-1(lf) mutants in behavior and synaptic transmission and suppressed the lethargy, egg-laying defect, and deficient neurotransmitter release caused by SLO-1(gf). In heterologous expression systems, BKIP-1 decreased the activation rate and shifted the conductance-voltage relationship of SLO-1 in a Ca²+-dependent manner and increased SLO-1 surface expression. Thus, BKIP-1 is a novel auxiliary subunit critical to SLO-1 function in vivo.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
authors.forename: Bojun
authors.initials: B
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Ge
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xia
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Sijie J
authors.initials: SJ
authors.lastname: Wang
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhan
authors.forename: Betty A
authors.initials: BA
authors.lastname: Eipper
authors.forename: Zhao-Wen
authors.initials: ZW
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D019921:Biotinylation / Q000379:methods; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D008124:Locomotion / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000502:physiology; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology*; D043762:Reproductive Behavior / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics; D014981:Xenopus
chemical_list: D029742:Caenorhabditis elegans Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008164:Luminescent Proteins; D021122:Protein Subunits; C494845:slo-1 protein, C elegans