dSLo interacting protein 1, a novel protein that interacts with large-conductance calcium-activated potassium channels.
Large-conductance calcium-activated potassium channels (BK channels) are activated by depolarized membrane potential and elevated levels of intracellular calcium. BK channel activity underlies the fast afterhyperpolarization that follows an action potential and attenuates neurotransmitter and hormone secretion. Using a modified two-hybrid approach, the interaction trap, we have identified a novel protein from Drosophila, dSLIP1 (dSLo interacting protein), which specifically interacts with Drosophila and human BK channels and has partial homology to the PDZ domain of alpha1 syntrophin. The dSLIP1 and dSlo mRNAs are expressed coincidently throughout the Drosophila nervous system, the two proteins interact in vitro, and they may be coimmunoprecipitated from transfected cells. Coexpression of dSLIP1 with dSlo or hSlo BK channels in Xenopus oocytes results in reduced currents as compared with expression of BK channels alone; current amplitudes may be rescued by coexpression with the channel domain that interacts with dSLIP1. Single-channel recordings and immunostaining of transfected tissue culture cells suggest that dSLIP1 selectively reduces Slo BK currents by reducing the number of BK channels in the plasma membrane.
Xia
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Xm
Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA.
Hirschberg
B
B
Smolik
S
S
Forte
M
M
Adelman
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D019556:COS Cells; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004330:Drosophila; D029721:Drosophila Proteins; D015870:Gene Expression; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D024681:Potassium Channels, Calcium-Activated; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection
D029721:Drosophila Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D018832:Molecular Chaperones; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; C111176:Slip1 protein, Drosophila; C494844:slo protein, Drosophila; D002118:Calcium