Universität zu Köln

Beqollari, Donald, Romberg, Christin F., Filipova, Dilyana ORCID: 0000-0003-3532-9765, Meza, Ulises, Papadopoulos, Symeon and Bannister, Roger A. (2015). Rem uncouples excitation-contraction coupling in adult skeletal muscle fibers. J. Gen. Physiol., 146 (1). S. 97 - 109. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-7748

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Abstract

In skeletal muscle, excitation-contraction (EC) coupling requires depolarization-induced conformational rearrangements in L-type Ca2+ channel (Ca(V)1.1) to be communicated to the type 1 ryanodine-sensitive Ca2+ release channel (RYR1) of the sarcoplasmic reticulum (SR) via transient protein-protein interactions. Although the molecular mechanism that underlies conformational coupling between Ca(V)1.1 and RYR1 has been investigated intensely for more than 25 years, the question of whether such signaling occurs via a direct interaction between the principal, voltage-sensing alpha(1S) subunit of Ca(V)1.1 and RYR1 or through an intermediary protein persists. A substantial body of evidence supports the idea that the auxiliary beta(1a) subunit of Ca(V)1.1 is a conduit for this intermolecular communication. However, a direct role for beta(1a) has been difficult to test because beta(1a) serves two other functions that are prerequisite for conformational coupling between Ca(V)1.1 and RYR1. Specifically, beta(1a) promotes efficient membrane expression of Ca(V)1.1 and facilitates the tetradic ultrastructural arrangement of Ca(V)1.1 channels within plasma membrane-SR junctions. In this paper, we demonstrate that overexpression of the RGK protein Rem, an established. subunit-interacting protein, in adult mouse flexor digitorum brevis fibers markedly reduces voltageinduced myoplasmic Ca2+ transients without greatly affecting Ca(V)1.1 targeting, intramembrane gating charge movement, or releasable SR Ca2+ store content. In contrast, a beta(1a)-binding-deficient Rem triple mutant (R200A/L227A/H229A) has little effect on myoplasmic Ca2+ release in response to membrane depolarization. Thus, Rem effectively uncouples the voltage sensors of Ca(V)1.1 from RYR1-mediated SR Ca2+ release via its ability to interact with beta(1a). Our findings reveal Rem-expressing adult muscle as an experimental system that may prove useful in the definition of the precise role of the beta(1a) subunit in skeletal-type EC coupling.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Beqollari, Donald UNSPECIFIED UNSPECIFIED UNSPECIFIED Romberg, Christin F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Filipova, Dilyana UNSPECIFIED orcid.org/0000-0003-3532-9765 UNSPECIFIED Meza, Ulises UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadopoulos, Symeon UNSPECIFIED UNSPECIFIED UNSPECIFIED Bannister, Roger A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-399751
DOI:	10.1085/jgp.201411314
Journal or Publication Title:	J. Gen. Physiol.
Volume:	146
Number:	1
Page Range:	S. 97 - 109
Date:	2015
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-7748
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language II-III LOOP; CHANNEL BETA-SUBUNIT; C-TERMINAL TAIL; DIHYDROPYRIDINE-RECEPTOR; CHARGE MOVEMENT; RYANODINE RECEPTOR-TYPE-1; ALPHA(1) SUBUNIT; CA2+ TRANSIENTS; CALCIUM-RELEASE; RGK PROTEINS Multiple languages Physiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39975