Anoctamin-6 controls bone mineralization by activating the calcium transporter NCX1.

ABSTRACT: Anoctamin-6 (Ano6, TMEM16F) belongs to a family of putative Ca(2+)-activated Cl(-) channels and operates as membrane phospholipid scramblase. Deletion of Ano6 leads to reduced skeleton size, skeletal deformities, and mineralization defects in mice. However, it remains entirely unclear how a lack of Ano6 leads to a delay in bone mineralization by osteoblasts. The Na(+)/Ca(2+) exchanger NCX1 was found to interact with Ano6 in a two-hybrid split-ubiquitin screen. Using human osteoblasts and osteoblasts from Ano6(-/-) and WT mice, we demonstrate that NCX1 requires Ano6 to efficiently translocate Ca(2+) out of osteoblasts into the calcifying bone matrix. Ca(2+)-activated anion currents are missing in primary osteoblasts isolated from Ano6 null mice. Our findings demonstrate the importance of NC

SUBMITTER: Ousingsawat J 

PROVIDER: S-EPMC4358264 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature