title: Role of the STIM1 C-terminal domain in STIM1 clustering.
abstract: Store-operated Ca(2+) entry (SOCE) represents a ubiquitous Ca(2+) influx pathway activated by the filling state of intracellular Ca(2+) stores. SOCE is mediated by coupling of STIM1, the endoplasmic reticulum Ca(2+) sensor, to the Orai1 channel. SOCE inactivates during meiosis, partly because of the inability of STIM1 to cluster in response to store depletion. STIM1 has several functional domains, including the Orai1 interaction domain (STIM1 Orai Activating Region (SOAR) or CRAC Activation Domain (CAD)) and STIM1 homomerization domain. When Ca(2+) stores are full, these domains are inactive to prevent constitutive Ca(2+) entry. Here we show, using the Xenopus oocyte as an expression system, that the C-terminal 200 residues of STIM1 are important to maintain STIM1 in an inactive state when Ca(2+) stores are full, through predicted intramolecular shielding of the active STIM1 domains (SOAR/CAD and STIM1 homomerization domain). Interestingly, our data argue that the C-terminal 200 residues accomplish this through a steric hindrance mechanism because they can be substituted by GFP or mCherry while maintaining all aspects of STIM1 function. We further show that STIM1 clustering inhibition during meiosis is independent of the C-terminal 200 residues.
authors.affiliation: From the Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation, Education City, Doha 24144, Qatar.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: From the Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation, Education City, Doha 24144, Qatar.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: From the Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation, Education City, Doha 24144, Qatar.
authors.forename: Raphael
authors.initials: R
authors.lastname: Courjaret
authors.affiliation: From the Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation, Education City, Doha 24144, Qatar. Electronic address: khm2002@qatar-med.cornell.edu.
authors.forename: Khaled
authors.initials: K
authors.lastname: Machaca
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008540:Meiosis / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000071740:ORAI1 Protein; D009865:Oocytes / Q000166:cytology; D055503:Protein Multimerization / Q000502:physiology*; D017434:Protein Structure, Tertiary; D000071737:Stromal Interaction Molecule 1; D014982:Xenopus laevis
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium