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Resources » Paper

Wang QC et al. (2016) Cell "TMCO1 Is an ER Ca(2+) Load-Activated Ca(2+) Channel."

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  • Comments on Wang QC et al. (2016) Cell "TMCO1 Is an ER Ca(2+) Load-Activated Ca(2+) Channel." (0)

  • Overview

    PMID:
    27212239
    DOI:
    10.1016/j.cell.2016.04.051
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00049701

    Wang QC, Zheng Q, Tan H, Zhang B, Li X, Yang Y, Yu J, Liu Y, Chai H, Wang X, Sun Z, Wang JQ, Zhu S, Wang F, Yang M, Guo C, Wang H, Li Y, Chen Q, Zhou A, & Tang TS (2016). TMCO1 Is an ER Ca(2+) Load-Activated Ca(2+) Channel. Cell, 165, 1454-66. doi:10.1016/j.cell.2016.04.051

    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 anddisassembly 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.

    Authors: Wang QC, Zheng Q, Tan H, Zhang B, Li X, Yang Y, Yu J, Liu Y, Chai H, Wang X, Sun Z, Wang JQ, Zhu S, Wang F, Yang M, Guo C, Wang H, Li Y, Chen Q, Zhou A, Tang TS


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