| First Author | Wang QC | Year | 2016 |
| Journal | Cell | Volume | 165 |
| Issue | 6 | Pages | 1454-1466 |
| PubMed ID | 27212239 | Mgi Jnum | J:233671 |
| Mgi Id | MGI:5787843 | Doi | 10.1016/j.cell.2016.04.051 |
| Citation | Wang QC, et al. (2016) TMCO1 Is an ER Ca(2+) Load-Activated Ca(2+) Channel. Cell 165(6):1454-66 |
| abstractText | Maintaining homeostasis of Ca(2+) stores in the endoplasmic reticulum (ER) is crucial for proper Ca(2+) signaling and key cellular functions. The Ca(2+)-release-activated Ca(2+) (CRAC) channel is responsible for Ca(2+) influx and refilling after store depletion, but how cells cope with excess Ca(2+) when ER stores are overloaded is unclear. We show that TMCO1 is an ER transmembrane protein that actively prevents Ca(2+) stores from overfilling, acting as what we term a "Ca(2+) load-activated Ca(2+) channel" or "CLAC" channel. TMCO1 undergoes reversible homotetramerization in response to ER Ca(2+) overloading and disassembly upon Ca(2+) depletion and forms a Ca(2+)-selective ion channel on giant liposomes. TMCO1 knockout mice reproduce the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, a developmental disorder linked to TMCO1 dysfunction, and exhibit severe mishandling of ER Ca(2+) in cells. Our findings indicate that TMCO1 provides a protective mechanism to prevent overfilling of ER stores with Ca(2+) ions. |
