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 I 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-K0 mice died. The SR swelled and developed large vacuoles in skeletal muscle cells just before the JP-1-K0 mice died. The present results strongly suggest that JP-I and JP-2 play important roles in the formation of triads and diads, respectively, during the development of skeletal muscle in mouse. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.