The Builders of the Junction: Roles of Junctophilin1 and Junctophilin2 in the Assembly of the Sarcoplasmic Reticulum–Plasma Membrane Junctions in Striated Muscle

Abstract

Contraction of striated muscle is triggered by a massive release of calcium from the sarcoplasmic reticulum (SR) into the cytoplasm. This intracellular calcium release is initiated by membrane depolarization, which is sensed by voltage-gated calcium channels CaV1.1 (in skeletal muscle) and CaV1.2 (in cardiac muscle) in the plasma membrane (PM), which in turn activate the calcium-releasing channel ryanodine receptor (RyR) embedded in the SR membrane. This cross-communication between channels in the PM and in the SR happens at specialized regions, the SR-PM junctions, where these two compartments come in close proximity. Junctophilin1 and Junctophilin2 are responsible for the formation and stabilization of SR-PM junctions in striated muscle and actively participate in the recruitment of the two essential players in intracellular calcium release, CaV and RyR. This short review focuses on the roles of junctophilins1 and 2 in the formation and organization of SR-PM junctions in skeletal and cardiac muscle and on the functional consequences of the absence or malfunction of these proteins in striated muscle in light of recently published data and recent advancements in protein structure prediction.

Transient receptor potential channel 6 in human skeletal muscle fibers: Investigation in fresh and conserved tissue samples

“…However the exact localization should be investigated further using high-dissolving techniques such as immune electron microscopy. The junctional sarcoplasmic reticulum including L-tubule and T-tubule and the triads play a major role in the electro-mechanical linkage and are areas where calcium channels are localized (14). For the non-junctional sarcoplasmic reticulum within striated muscles, it has been demonstrated in 293 cells that TRPC channels interact with the proteins junctate and inositol-1,4,5-triphosphate receptor (15).…”

Excitation-contraction coupling in mammalian skeletal muscle: Blending old and last-decade research

“…There is debate on whether JPH-2 interacts or not with RyR1 (Phimister et al, 2007;Nakada et al, 2018). The ability of JPH-1 and -2 to regulate Ca 2+ release in myotubes likely relies on their DHPRbinding ability and their TT-jSR tethering properties, which also mediate the precise localization of CRU (Nakada et al, 2018;Perni, 2022).…”

Proteomic profiling of impaired excitation–contraction coupling and abnormal calcium handling in muscular dystrophy

“…Importantly, the isoform expression pattern of many Ca 2+ -regulatory proteins differs between fast-twitching versus slow-twitching muscle fibres [82], making them ideal markers of muscle fibre type shifting in neuromuscular diseases [83]. A variety of minor junctional proteins are involved in triad architecture and stabilisation of the depolarisation-induced Ca 2+ -release mechanism including triadin, junctin, juntophilin-1, junctophilin-2 and mitsugumin MG-29 [84][85][86][87], as reviewed by Treves et al [88]. Additional Ca 2+ -regulatory elements are represented by the stromal interaction molecule STIM1, the calcium release-activated calcium modulator ORAI1, the SH3 and cysteine-rich domain-containing protein STAC3 and various Ca 2+ -leak channels [89][90][91], as well as intracellular organelle proteins such as the mitochondrial Na + /Ca + -exchanger, H + /Ca 2+ -exchanger, Ca 2+ -uniporter complex and the porin VDAC (voltage-dependent anion channel) complex [92,93].…”