Abstract:
:The trimeric intracellular cation (TRIC) channels TRIC-A and TRIC-B localize predominantly to the endoplasmic reticulum (ER) and likely support Ca(2+) 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 Ca(2+) release from ER and increased ER Ca(2+) 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.
journal_name
Sci Signaljournal_title
Science signalingauthors
Zhao C,Ichimura A,Qian N,Iida T,Yamazaki D,Noma N,Asagiri M,Yamamoto K,Komazaki S,Sato C,Aoyama F,Sawaguchi A,Kakizawa S,Nishi M,Takeshima Hdoi
10.1126/scisignal.aad9055subject
Has Abstractpub_date
2016-05-17 00:00:00pages
ra49issue
428eissn
1945-0877issn
1937-9145pii
9/428/ra49journal_volume
9pub_type
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