title: Inositol 1,4,5-trisphosphate receptor and dSTIM function in Drosophila insulin-producing neurons regulates systemic intracellular calcium homeostasis and flight.
abstract: Calcium (Ca(2+)) signaling is known to regulate the development, maintenance and modulation of activity in neuronal circuits that underlie organismal behavior. In Drosophila, intracellular Ca(2+) signaling by the inositol 1,4,5-trisphosphate receptor and the store-operated channel (dOrai) regulates the formation and function of neuronal circuits that control flight. Here, we show that restoring InsP(3)R activity in insulin-producing neurons of flightless InsP(3)R mutants (itpr) during pupal development can rescue systemic flight ability. Expression of the store operated Ca(2+) entry (SOCE) regulator dSTIM in insulin-producing neurons also suppresses compromised flight ability of InsP(3)R mutants suggesting that SOCE can compensate for impaired InsP(3)R function. Despite restricted expression of wild-type InsP(3)R and dSTIM in insulin-producing neurons, a global restoration of SOCE and store Ca(2+) is observed in primary neuronal cultures from the itpr mutant. These results suggest that restoring InsP(3)R-mediated Ca(2+) release and SOCE in a limited subset of neuromodulatory cells can influence systemic behaviors such as flight by regulating intracellular Ca(2+) homeostasis in a large population of neurons through a non-cell-autonomous mechanism.
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Agrawal
authors.forename: Gayatri
authors.initials: G
authors.lastname: Venkiteswaran
authors.forename: Sufia
authors.initials: S
authors.lastname: Sadaf
authors.forename: Nisha
authors.initials: N
authors.lastname: Padmanabhan
authors.forename: Santanu
authors.initials: S
authors.lastname: Banerjee
authors.forename: Gaiti
authors.initials: G
authors.lastname: Hasan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005426:Flight, Animal / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007424:Intracellular Fluid / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011679:Pupa / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1
chemical_list: D029721:Drosophila Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007328:Insulin; D008565:Membrane Proteins; C502662:Stim protein, Drosophila; D000071737:Stromal Interaction Molecule 1; D002118:Calcium