Key result
In zebrafish muscle fibers, DHPR is transported along the longitudinal sarcoplasmic reticulum in a microtubule-independent mechanism that requires the beta subunit but not Stac3.
The study reveals previously unappreciated features of DHPR motility within the sarcoplasmic reticulum prior to assembly at triads in skeletal muscle.
No immediate clinical implications; leaves open whether beta subunit dependence extends to mammalian cardiac muscle.
Contraction of skeletal muscle is initiated by excitation‐contraction ( EC ) coupling during which membrane voltage is transduced to intracellular Ca 2+ release. EC coupling requires L‐type voltage gated Ca 2 + channels (the dihydropyridine receptor or DHPR ) located at triads, which are junctions between the transverse (T) tubule and sarcoplasmic reticulum ( 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.
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Linsley et al. (2017) studied this question. Stac3 or DHPRβ null mutations vs. Wild-type was evaluated on DHPR transport mechanism and localization. In zebrafish muscle fibers, DHPR is transported along the longitudinal sarcoplasmic reticulum in a microtubule-independent mechanism that requires the beta subunit but not Stac3.
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