Specific interaction of the potassium channel β-subunit minK with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system

Tetsushi Furukawa, Yasuko Ono, Hiroyuki Tsuchiya, Yoshifumi Katayama, Marie Louise Bang, Dietmar Labeit, Siegfried Labeit, Nobuya Inagaki, Carol C. Gregorio

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

Ion-channel β-subunits are ancillary proteins that co-assemble with α-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 β-subunit of the slow activating component of the delayed rectifier potassium current (IKs) channel, and associates with the α-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 β-subunit of the IKs 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.

Original languageEnglish (US)
Pages (from-to)775-784
Number of pages10
JournalJournal of Molecular Biology
Volume313
Issue number4
DOIs
StatePublished - Nov 2 2001

Keywords

  • MinK
  • T-cap/telethonin
  • T-tubules
  • Titin
  • Z-lines

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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