First Author | Kim H | Year | 2013 |
Journal | Cell Metab | Volume | 17 |
Issue | 2 | Pages | 249-60 |
PubMed ID | 23395171 | Mgi Jnum | J:198051 |
Mgi Id | MGI:5495340 | Doi | 10.1016/j.cmet.2013.01.002 |
Citation | Kim H, et al. (2013) Tmem64 modulates calcium signaling during RANKL-mediated osteoclast differentiation. Cell Metab 17(2):249-60 |
abstractText | Osteoclast maturation and function primarily depend on receptor activator of NF-kappaB ligand (RANKL)-mediated induction of nuclear factor of activated T cells c1 (NFATc1), which is further activated via increased intracellular calcium ([Ca(2+)](i)) oscillation. However, the coordination mechanism that mediates Ca(2+) oscillation during osteoclastogenesis remains ill defined. Here, we identified transmembrane protein 64 (Tmem64) as a regulator of Ca(2+) oscillation during osteoclastogenesis. We found that Tmem64-deficient mice exhibit increased bone mass due in part to impaired osteoclast formation. Using in vitro osteoclast culture systems, we show here that Tmem64 interacts with sarcoplasmic endoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) and modulates its activity. Consequently, Tmem64 deficiency significantly diminishes RANKL-induced [Ca(2+)](i) oscillation, which results in reduced Ca(2+)/calmodulin-dependent protein kinases (CaMK) IV and mitochondrial ROS, both of which contribute to achieving the CREB activity necessary for osteoclast formation. These data demonstrate that Tmem64 is a positive modulator of osteoclast differentiation via SERCA2-dependent Ca(2+) signaling. |