Ichimura Atsuhiko, Takeshima Hiroshi
Graduate School of Pharmaceutical Sciences, Kyoto University.
Biol Pharm Bull. 2016;39(11):1743-1747. doi: 10.1248/bpb.b16-00612.
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 Ca 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.
三聚体细胞内阳离子（TRIC）通道亚型，即TRIC-A和TRIC-B，在内质网/肌浆网和核膜中表达，并且可能在各种细胞类型中作为单价阳离子通道发挥作用。我们目前使用基因敲除小鼠进行的研究表明，TRIC亚型通过介导反阳离子通量来支持细胞内钙库的钙释放。最近在常染色体隐性遗传性成骨不全症（OI）患者中发现了TRIC-B基因座内的几种基因突变。然而，这些突变导致人类疾病的分子机制尚未得到充分研究。我们发现Tric-b基因敲除小鼠表现出骨矿化不良，因此可作为OI模型动物。目前对Tric-b基因敲除小鼠的骨骼以及从患者中获得的培养细胞系的研究揭示了TRIC-B突变型OI形式所涉及的病理生理机制的主要部分。这篇小型综述聚焦于TRIC-B通道在骨矿化中的重要作用。
