Identification and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in rat brain

다국어 초록 (Multilingual Abstract)

<P>Abstract</P><P>Large-conductance Ca<SUP>2+</SUP>-activated K<SUP>+</SUP> (BK<SUB>Ca</SUB>) channels are activated by membrane depolarization and modulated by intracellular Ca<SUP>2+</SUP>. Here, we report the direct interaction of cereblon (CRBN) with the cytosolic carboxy-terminus of the BK<SUB>Ca</SUB> channel &agr; subunit (Slo). Rat CRBN contained the N-terminal domain of the Lon protease, a ‘regulators of G protein-signaling’ (RGS)-like domain, a leucine zipper (LZ) motif, and four putative protein kinase C (PKC) phosphorylation sites. RNA messages of rat cereblon (rCRBN) were widely distributed in different tissues with especially high-levels of expression in the brain. Direct association of rCRBN with the BK<SUB>Ca</SUB> channel was confirmed by immunoprecipitation in brain lysate, and the two proteins were co-localized in cultured rat hippocampal neurons. Ionic currents evoked by the rSlo channel were dramatically suppressed upon coexpression of rCRBN. rCRBN decreased the formation of the tetrameric rSlo complex thus reducing the surface expression of functional channels. Therefore, we suggest that CRBN may play an important role in assembly and surface expression of functional BK<SUB>Ca</SUB> channels by direct interaction with the cytosolic C-terminus of its &agr;-subunit.</P>