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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Behavior, Animal
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Biotinylation / methods
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / physiology*
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Excitatory Postsynaptic Potentials / genetics
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Humans
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Immunoprecipitation / methods
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Large-Conductance Calcium-Activated Potassium Channels / chemistry*
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Large-Conductance Calcium-Activated Potassium Channels / genetics
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Large-Conductance Calcium-Activated Potassium Channels / physiology*
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Locomotion / genetics
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Luminescent Proteins / genetics
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Models, Molecular
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Molecular Sequence Data
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Mutation / genetics
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Neurons / physiology
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Oocytes
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Patch-Clamp Techniques / methods
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Protein Subunits / genetics
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Protein Subunits / physiology*
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Reproductive Behavior / physiology
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Synaptic Transmission / genetics
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Xenopus
Substances
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Caenorhabditis elegans Proteins
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Large-Conductance Calcium-Activated Potassium Channels
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Luminescent Proteins
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Protein Subunits
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slo-1 protein, C elegans