TRIC-B Mutations Causing Osteogenesis Imperfecta.
Trimeric intracellular cation (TRIC) channel subtypes, namely TRIC-A and TRIC-B, are expressed in the endoplasmic/sarcoplasmic reticulum and nuclear envelope, and likely function as monovalent cation channels in various cell types. Our studies using knockout mice so far suggest that TRIC subtypes support Ca2+release from intracellular stores by mediating counter-cationic fluxes. Several genetic mutations within the TRIC-B locus were recently identified in autosomal recessive osteogenesis imperfecta (OI) patients. However, the molecular mechanism by which the mutations cause human disease is not fully addressed. We found that Tric-b-knockout mice exhibit poor bone ossification and thus serve as an OI-model animal. Studies on Tric-b-knockout bones and cultured cell lines derived from the patients currently reveal the main part of the pathophysiological mechanism involved in the TRIC-B-mutated OI form. This mini-review focuses on the essential role of TRIC-B channels in bone ossification.
Graduate School of Pharmaceutical Sciences, Kyoto University.
Atsuhiko
A
Ichimura
Hiroshi
H
Takeshima
D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics*
D007473:Ion Channels; C578840:TMEM38B protein, human; C522222:TRIC-B protein, mouse