PUBLICATION

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

Authors
Linsley, J.W., Hsu, I.U., Wang, W., Kuwada, J.Y.
ID
ZDB-PUB-170712-3
Date
2017
Source
Traffic (Copenhagen, Denmark)   18(9): 622-632 (Journal)
Registered Authors
Kuwada, John
Keywords
DHPR, EC coupling, Stac3, calcium channel, skeletal muscle, trafficking, zebrafish
MeSH Terms
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Calcium/metabolism
  • Calcium Channels, L-Type/metabolism*
  • Cells, Cultured
  • Excitation Contraction Coupling/physiology
  • Muscle Fibers, Skeletal/metabolism
  • Muscle Proteins/metabolism
  • Muscle, Skeletal/metabolism*
  • Sarcoplasmic Reticulum/metabolism*
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed
28697281 Full text @ Traffic
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 L-type voltage gated Ca2+ 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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes