title: Store-independent modulation of Ca(2+) entry through Orai by Septin 7.
abstract: Orai channels are required for store-operated Ca(2+) entry (SOCE) in multiple cell types. Septins are a class of GTP-binding proteins that function as diffusion barriers in cells. Here we show that Septin 7 acts as a 'molecular brake' on activation of Orai channels in Drosophila neurons. Lowering Septin 7 levels results in dOrai-mediated Ca(2+) entry and higher cytosolic Ca(2+) in resting neurons. This Ca(2+) entry is independent of depletion of endoplasmic reticulum Ca(2+) stores and Ca(2+) release through the inositol-1,4,5-trisphosphate receptor. Importantly, store-independent Ca(2+) entry through Orai compensates for reduced SOCE in the Drosophila flight circuit. Moreover, overexpression of Septin 7 reduces both SOCE and flight duration, supporting its role as a negative regulator of Orai channel function in vivo. Septin 7 levels in neurons can, therefore, alter neural circuit function by modulating Orai function and Ca(2+) homeostasis.
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore 560065, India.
authors.forename: Bipan Kumar
authors.initials: BK
authors.lastname: Deb
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore 560065, India.|Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Trayambak
authors.initials: T
authors.lastname: Pathak
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore 560065, India.
authors.forename: Gaiti
authors.initials: G
authors.lastname: Hasan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005426:Flight, Animal / Q000502:physiology; D005786:Gene Expression Regulation; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000071740:ORAI1 Protein / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D058112:Septins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D000071740:ORAI1 Protein; D020033:Protein Isoforms; C510747:olf186-F protein, Drosophila; D015544:Inositol 1,4,5-Trisphosphate; D058112:Septins; D002118:Calcium