Minor sarcoplasmic reticulum membrane components that modulate excitation-contraction coupling in striated muscles

Abstract

In striated muscle, activation of contraction is initiated by membrane depolarisation caused by an action potential, which triggers the release of Ca(2+) stored in the sarcoplasmic reticulum by a process called excitation-contraction coupling. Excitation-contraction coupling occurs via a highly sophisticated supramolecular signalling complex at the junction between the sarcoplasmic reticulum and the transverse tubules. It is generally accepted that the core components of the excitation-contraction coupling machinery are the dihydropyridine receptors, ryanodine receptors and calsequestrin, which serve as voltage sensor, Ca(2+) release channel, and Ca(2+) storage protein, respectively. Nevertheless, a number of additional proteins have been shown to be essential both for the structural formation of the machinery involved in excitation-contraction coupling and for its fine tuning. In this review we discuss the functional role of minor sarcoplasmic reticulum protein components. The definition of their roles in excitation-contraction coupling is important in order to understand how mutations in genes involved in Ca(2+) signalling cause neuromuscular disorders.

Figure 1

Schematic representation of the protein components of skeletal muscle sarcoplasmic reticulum

Figure 2. Coomassie Brilliant Blue stained gradient (5–15%) SDS-PAGE of protein components present in the longitudinal sarcoplasmic reticulum (LSR), in terminal cisternae (TC) and in the junctional face membrane (JFM) fractions obtained from rabbit SR

Reproduced from Fig. 2 of Zorzato et al. (1986).

Figure 3. Genomic organization, splicing pattern and main protein products deriving from of the A-β-J-J locus

A, coloured boxes represent different exons. Products deriving from exon 1 (green box) give rise to β-aspartyl-hydroxylase/humbug; products deriving from exon 1b (light blue) give rise to junctin/junctate. Yellow box encodes the transmembrane domain. Reproduced from Fig. 4 of Dinchunk et al. 2000. B, schematic representation of the 4 main proteins (junctin, junctate, aspartyl-β-hydroxylase and humbug) derived by assembling the different exons (colours of the protein domains match those of the exons from which they are derived).