Deficiency of triad formation in developing skeletal muscle cells lacking junctophilin type 1.

Junctophilins (JP-1, JP-2, and JP-3) are transmembrane proteins expressed in the junctional membrane complexes in excitable cells. Both JP-1 and JP-2 are co-expressed in the triads of skeletal muscle, but only JP-2 is expressed in cardiac muscle. We analyzed the roles played by JP-1 and JP-2 in triad formation in skeletal muscle by comparing developing skeletal muscles in wild-type and JP-1-knockout (KO) mice (both before and after birth). In the skeletal muscles of embryos, most of the couplings between sarcoplasmic reticulum (SR) and transverse tubule (T-tubule) were diads, with triads being very scarce. The number of triads increased markedly after birth in wild-type mice. However, there was no increase in the number of triads in the neonates of JP-1-KO mice, and they died within 1 day after birth. JP-2 expression was constant before and after birth, while expression of JP-1 increased with birth. Quantitative and morphological differences were not seen between wild-type and JP-1-KO mice in the formation of diads in the period just before the JP-1-KO mice died. The SR swelled and developed large vacuoles in skeletal muscle cells just before the JP-1-KO mice died. The present results strongly suggest that JP-1 and JP-2 play important roles in the formation of triads and diads, respectively, during the development of skeletal muscle in mouse.