| First Author | Ma G | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7826 | PubMed ID | 26184105 |
| Mgi Jnum | J:224453 | Mgi Id | MGI:5662311 |
| Doi | 10.1038/ncomms8826 | Citation | Ma G, et al. (2015) Inside-out Ca(2+) signalling prompted by STIM1 conformational switch. Nat Commun 6:7826 |
| abstractText | Store-operated Ca(2+) entry mediated by STIM1 and ORAI1 constitutes one of the major Ca(2+) entry routes in mammalian cells. The molecular choreography of STIM1-ORAI1 coupling is initiated by endoplasmic reticulum (ER) Ca(2+) store depletion with subsequent oligomerization of the STIM1 ER-luminal domain, followed by its redistribution towards the plasma membrane to gate ORAI1 channels. The mechanistic underpinnings of this inside-out Ca(2+) signalling were largely undefined. By taking advantage of a unique gain-of-function mutation within the STIM1 transmembrane domain (STIM1-TM), here we show that local rearrangement, rather than alteration in the oligomeric state of STIM1-TM, prompts conformational changes in the cytosolic juxtamembrane coiled-coil region. Importantly, we further identify critical residues within the cytoplasmic domain of STIM1 (STIM1-CT) that entail autoinhibition. On the basis of these findings, we propose a model in which STIM1-TM reorganization switches STIM1-CT into an extended conformation, thereby projecting the ORAI-activating domain to gate ORAI1 channels. |
