Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1

Citation
K. Ito et al., Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1, J CELL BIOL, 154(5), 2001, pp. 1059-1067
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
5
Year of publication
2001
Pages
1059 - 1067
Database
ISI
SICI code
0021-9525(20010903)154:5<1059:DOTJAC>2.0.ZU;2-Q
Abstract
In skeletal muscle excitation-contraction (E-C) coupling, the depolarizatio n signal is converted from the intracellular Ca2+ store into Ca2+ release b y functional coupling between the cell surface voltage sensor and the Ca2release channel on the sarcoplasmic reticulum (SR). The signal conversion o ccurs in the junctional membrane complex known as the triad junction, where the invaginated plasma membrane called the transverse-tubule (T-tubule) is pinched from both sides by SR membranes. Previous studies have suggested t hat junctophilins (JPs) contribute to the formation of the junctional membr ane complexes by spanning the intracellular store membrane and interacting with the plasma membrane (PM) in excitable cells. Of the three JP subtypes, both type 1 (JP-1) and type 2 (JP-2) are abundantly expressed in skeletal muscle. To examine the physiological role of JP-1 in skeletal muscle, we ge nerated mutant mice lacking JP-1. The JP-1 knockout mice showed no milk suc kling and died shortly after birth. Ultrastructural analysis demonstrated t hat triad junctions were reduced in number, and that the SR was often struc turally abnormal in the skeletal muscles of the mutant mice. The mutant mus cle developed less contractile force (evoked by low-frequency electrical st imuli) and showed abnormal sensitivities to extracellular Ca2+. Our results indicate that JP-1 contributes to the construction of triad junctions and that it is essential for the efficiency of signal conversion during E-C cou pling in skeletal muscle.