Inositol 1,4,5-trisphosphate receptor and dSTIM function in Drosophila insulin-producing neurons regulates systemic intracellular calcium homeostasis and flight

Abstract

Calcium (Ca²⁺) signaling is known to regulate the development, maintenance and modulation of activity in neuronal circuits that underlie organismal behavior. In Drosophila, intracellular Ca²⁺ 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 InsP₃R activity in insulin-producing neurons of flightless InsP₃R mutants (itpr) during pupal development can rescue systemic flight ability. Expression of the store operated Ca²⁺ entry (SOCE) regulator dSTIM in insulin-producing neurons also suppresses compromised flight ability of InsP₃R mutants suggesting that SOCE can compensate for impaired InsP₃R function. Despite restricted expression of wild-type InsP₃R and dSTIM in insulin-producing neurons, a global restoration of SOCE and store Ca²⁺ is observed in primary neuronal cultures from the itpr mutant. These results suggest that restoring InsP₃R-mediated Ca²⁺ release and SOCE in a limited subset of neuromodulatory cells can influence systemic behaviors such as flight by regulating intracellular Ca²⁺ homeostasis in a large population of neurons through a non-cell-autonomous mechanism.