期刊
SCIENCE SIGNALING
卷 9, 期 428, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aad9055
关键词
-
资金
- MEXT (Ministry of Education, Culture, Sports, Science and Technology)/JSPS (Japan Society for the Promotion of Science) (KAKENHI) [15H04676, 26670028, 15H05652]
- Takeda Science Foundation
- Kobayashi International Scholarship Foundation
- Nakatomi Foundation
- Salt Science Research Foundation
- Vehicle Racing Commemorative Foundation
- Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX)
- Japan Foundation for Applied Enzymology
- Grants-in-Aid for Scientific Research [15K06774, 14J06672, 15H04676, 15H05652, 26670028, 16H01562, 15K14499] Funding Source: KAKEN
The trimeric intracellular cation (TRIC) channels TRIC-A and TRIC-B localize predominantly to the endoplasmic reticulum (ER) and likely support Ca2+ release from intracellular stores by mediating cationic flux to maintain electrical neutrality. Deletion and point mutations in TRIC-B occur in families with autosomal recessive osteogenesis imperfecta. Tric-b knockout mice develop neonatal respiratory failure and exhibit poor bone ossification. We investigated the cellular defect causing the bone phenotype. Bone histology indicated collagen matrix deposition was reduced in Tric-b knockout mice. Osteoblasts, the bone-depositing cells, from Tric-b knockout mice exhibited reduced Ca2+ release from ER and increased ER Ca2+ content, which was associated with ER swelling. These cells also had impaired collagen release without a decrease in collagen-encoding transcripts, consistent with a defect in trafficking of collagen through ER. In contrast, osteoclasts, the bone-degrading cells, from Tric-b knockout mice were similar to those from wild-type mice. Thus, TRIC-B function is essential to support the production and release of large amounts of collagen by osteoblasts, which is necessary for bone mineralization.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据