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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism*
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Calcium Signaling*
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / genetics*
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Drosophila melanogaster / growth & development
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Drosophila melanogaster / metabolism
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Flight, Animal / physiology
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Gene Expression Regulation
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Inositol 1,4,5-Trisphosphate / metabolism
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Inositol 1,4,5-Trisphosphate Receptors / genetics
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Inositol 1,4,5-Trisphosphate Receptors / metabolism
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Larva / genetics
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Larva / growth & development
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Larva / metabolism
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Neurons / cytology
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Neurons / metabolism*
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ORAI1 Protein / genetics*
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ORAI1 Protein / metabolism
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Primary Cell Culture
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Septins / genetics*
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Septins / metabolism
Substances
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Drosophila Proteins
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Inositol 1,4,5-Trisphosphate Receptors
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ORAI1 Protein
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Protein Isoforms
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olf186-F protein, Drosophila
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Inositol 1,4,5-Trisphosphate
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Septins
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Calcium