Junctional Sarcoplasmic Reticulum Proteins in Skeletal Muscle Fibers

Sarcoplasmic Reticulum (SR) Organization

  • SR is a specialized endoplasmic reticulum in striated muscles for Ca2+Ca^{2+} release, activating muscle contraction.
  • It forms a network of longitudinal tubules and cisternae around myofibrils, assembling triadic junctional membrane complexes.

Longitudinal SR (l-SR)

  • Largest part of SR, tubules around myofibrils.
  • Main site for Ca2+Ca^{2+} storage and uptake via SERCA pumps.
  • High density near Z-disks, joining into terminal cisternae at A-I band junctions.

Junctional SR (j-SR)

  • Region of terminal cisternae facing t-tubules at triads.
  • Contains RyR1 and other proteins regulating Ca2+Ca^{2+} release.

sAnk1 and Obscurin

  • sAnk1 is a transmembrane protein on l-SR tubules that interacts with obscurin (a myofibrillar protein).
  • The interaction stabilizes l-SR tubules along myofibrils.

Triadin

  • Integral membrane protein at j-SR.
  • Contains multiple KEKE motifs for binding to calsequestrin (CASQ) and RyR1.
  • Facilitates depolarization-induced Ca2+Ca^{2+} release.

Junctin

  • Contains KEKE motifs and interacts with CASQs, RyRs, and triadin.
  • Contributes to maintaining SR Ca2+Ca^{2+} store size.

JP-45

  • Interacts with DHPR and CASQ.
  • Ablation leads to loss of skeletal muscle strength.

Calsequestrin

  • Most abundant Ca2+Ca^{2+} binding protein in SR, buffering free Ca2+Ca^{2+} to ~1 mM.
  • Exists as monomers or polymers depending on Ca2+Ca^{2+} concentration.

T-tubule Biogenesis

  • Starts in embryonic life, forming invaginations at the periphery of developing muscle fibers.
  • Association with SR occurs early, forming peripheral coupling and diads.

Junctophilins (JPHs)

  • Mediate association of t-tubules and SR membranes.
  • JPH1 and JPH2 isoforms in skeletal muscle.
  • JPH1 present throughout RyR1 arrays, JPH2 in smaller nanodomains.

Mitochondria and SR

  • Mitochondria localized near triads, facilitating Ca2+Ca^{2+} transfer.
  • Organelle tethers stabilize SR-mitochondria contacts.

Molecular Mechanisms of Excitation-Contraction Coupling

  • Requires precise structural arrangement.
  • Junctophilins are main players in triad assembly.