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  • Title: Specific interaction of the potassium channel beta-subunit minK with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system.
    Author: Furukawa T, Ono Y, Tsuchiya H, Katayama Y, Bang ML, Labeit D, Labeit S, Inagaki N, Gregorio CC.
    Journal: J Mol Biol; 2001 Nov 02; 313(4):775-84. PubMed ID: 11697903.
    Abstract:
    Ion-channel beta-subunits are ancillary proteins that co-assemble with alpha-subunits to modulate gating kinetics and enhance stability of multimeric channel complexes. They provide binding sites for other regulatory proteins and are medically important as the targets of many pharmacological compounds. MinK is the beta-subunit of the slow activating component of the delayed rectifier potassium current (I(Ks)) channel, and associates with the alpha-subunit, KvLQT1. We report here that minK specifically interacts with the sarcomeric Z-line component, T-cap (also called telethonin). In vitro interaction studies indicated that the cytoplasmic domain of minK specifically binds to the sixteen C-terminal residues of T-cap; these residues are sufficient for its interaction with minK. Consistent with our in vitro studies, immunofluorescence staining followed by confocal analysis revealed that both minK and T-cap are localized within the Z-line region in cardiac muscle. Striated staining of minK was observed in non-washed, membrane-intact cardiac myofibrils, but not in well-washed, membrane-removed cardiac myofibrils, suggesting that minK localizes on T-tubular membranes surrounding the Z-line in the inner ventricular myocardium. Together with our previous data on the colocalization and interaction of T-cap with the N-terminus of the giant protein titin in the periphery of the Z-line, these data suggest that T-cap functions as an adapter protein to link together myofibrillar components with the membranous beta-subunit of the I(Ks) channel. We speculate that this interaction may contribute to a stretch-dependent regulation of potassium flux in cardiac muscle, providing a "mechano-electrical feedback" system.
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