Official websites use. Share sensitive information only on official, secure websites. Author contributions: conceptualization, J. Marty isabelle. This article is distributed by The American Society for Cell Biology under license from the author s. Two months after publication it is available to the public under an Attribution—Noncommercial—Share Alike 3. In skeletal muscle, proteins of the calcium release complex responsible for the excitation-contraction EC coupling are exclusively localized in specific reticulum—plasma membrane ER-PM contact points named triads.
The CRC protein triadin T95 is localized in the sarcoplasmic reticulum SR subdomain of triads where it forms large multimers. However, the mechanisms leading to the steady-state accumulation of T95 in these specific areas of SR are largely unknown. At all stages of skeletal muscle cells differentiation, we show a permanent flux of T95 diffusing in the SR membrane.
Moreover, we find evidence that a longer residence time in the ER-PM contact point is due to the transmembrane domain of T95 resulting in an overall triad localization. Skeletal muscle contraction is triggered by a massive calcium release from intracellular stores upon plasma membrane depolarization. This phenomenon, known as the excitation-contraction EC coupling, occurs in specific sites of skeletal muscle, the triads.
Each triad consists of two reticulum terminal cisternae, the junctional sarcoplasmic reticulum jSR , flanking a single invagination of the plasma membrane, the transverse-tubule T-tubule Flucher, From a structural point of view, triads are contact points between T-tubule membranes and the jSR, where proteins of the multimolecular calcium release complex CRC are located. The sharp organization of T-tubule and jSR membranes is of outmost importance because it allows a physical cross-talk between the two main components of the CRC that are each anchored in a different membrane compartment: the voltage-gated channel dihydropyridine receptor DHPR in the T-tubule and the intracellular calcium channel ryanodine receptor 1 RyR1 in the jSR Franzini-Armstrong and Jorgensen, As a consequence of this organization, the structural modification of DHPR induced by membrane depolarization can mechanically trigger the opening of RyR1 Marty et al.
In addition to both channels, the CRC includes several regulatory proteins such as calsequestrin, junctin, triadin, which can modulate RyR1 function or the organization of the molecular complex. Interestingly in skeletal muscles, all proteins of the CRC are exclusively localized in the triad membranes Flucher, , without a clear view on the underlying mechanisms.
