title: An essential and NSF independent role for α-SNAP in store-operated calcium entry.
abstract: Store-operated calcium entry (SOCE) by calcium release activated calcium (CRAC) channels constitutes a primary route of calcium entry in most cells. Orai1 forms the pore subunit of CRAC channels and Stim1 is the endoplasmic reticulum (ER) resident Ca(2+) sensor. Upon store-depletion, Stim1 translocates to domains of ER adjacent to the plasma membrane where it interacts with and clusters Orai1 hexamers to form the CRAC channel complex. Molecular steps enabling activation of SOCE via CRAC channel clusters remain incompletely defined. Here we identify an essential role of α-SNAP in mediating functional coupling of Stim1 and Orai1 molecules to activate SOCE. This role for α-SNAP is direct and independent of its known activity in NSF dependent SNARE complex disassembly. Importantly, Stim1-Orai1 clustering still occurs in the absence of α-SNAP but its inability to support SOCE reveals that a previously unsuspected molecular re-arrangement within CRAC channel clusters is necessary for SOCE. DOI:http://dx.doi.org/10.7554/eLife.00802.001.
authors.affiliation: Pathology and Immunology , Washington University School of Medicine , St Louis , United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Miao
authors.forename: Cathrine
authors.initials: C
authors.lastname: Miner
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Phyllis I
authors.initials: PI
authors.lastname: Hanson
authors.forename: Adish
authors.initials: A
authors.lastname: Dani
authors.forename: Monika
authors.initials: M
authors.lastname: Vig
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004330:Drosophila; D006801:Humans; D017136:Ion Transport; D050778:NFATC Transcription Factors / Q000378:metabolism; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000378:metabolism* / Q000502:physiology*
chemical_list: D050778:NFATC Transcription Factors; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D002118:Calcium
keywords: CRAC channel; D. melanogaster; Human; Orai; SNAP; SOCE; Stim; calcium