Transport of the alpha subunit of the L ‐type calcium channel through the sarcoplasmic reticulum occurs prior to localization to triads and requires the beta subunit but not Stac3 in skeletal muscles

Abstract
Contraction of skeletal muscle is initiated by excitation‐contraction (EC) coupling during which membrane voltage is transduced to intracellular Ca2+ release. EC coupling requires dihydropyridine receptors (DHPR) located at triads, which are junctions between the transverse (T) tubule and SR membranes, that sense membrane depolarization in the T tubule membrane. Reduced EC coupling is associated with ageing, and disruptions of EC coupling result in congenital myopathies for which there are few therapies. The precise localization of DHPRs to triads is critical for EC coupling, yet trafficking of the DHPR to triads is not well understood. Using dynamic imaging of zebrafish muscle fibers we find that DHPR is transported along the longitudinal SR in a microtubule independent mechanism. Furthermore, transport of DHPR in the SR membrane is differentially affected in null mutants of Stac3 or DHPRβ, two essential components of EC coupling. These findings reveal previously unappreciated features of DHPR motility within the SR prior to assembly at triads.

Synopsis
Subcellular localization of DHPR at triadic junctions in skeletal muscle is required for EC‐coupling. We find that DHPR is transported via sarcoplasmic membrane to triads independent of microtubules. There appears also to be ER exit sites in the triads and nearby local Golgi outposts. Furthermore, SR trafficking of DHPR to triads is differentially affected in null mutations of Stac3 or DHPRβ, two essential com...

Source: Traffic - July 1, 2017 Category: Research Authors: Jeremy W. Linsley, I ‐Uen Hsu, Wenjai Wang, John Y. Kuwada Tags: ORIGINAL ARTICLE Source Type: research