Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 313, Issue 4, Pages 775-784Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1006/jmbi.2001.5053
Keywords
minK; T-cap/telethonin; titin; Z-lines; T-tubules
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Funding
- NHLBI NIH HHS [HL03985, HL63926] Funding Source: Medline
- NIEHS NIH HHS [ES-06694] Funding Source: Medline
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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 a-re 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. (C) 2001 Academic Press.
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