The enigma of store-operated Ca²⁺-entry in neurons: Answers from the Drosophila flight circuit

Abstract

In neurons a well-defined source of signaling Ca²⁺ is the extracellular medium. However, as in all metazoan cells, Ca²⁺ is also stored in endoplasmic reticular compartments inside neurons. The relevance of these stores in neuronal function has been debatable. The Orai gene encodes a channel that helps refill these stores from the extracellular medium in non-excitable cells through a process called store-operated Ca²⁺ entry or SOCE. Recent findings have shown that raising the level of Orai or its activator STIM, and consequently SOCE in neurons, can restore flight to varying extents to Drosophila mutants for an intracellular Ca²⁺-release channel - the inositol 1,4,5-trisphosphate receptor (InsP₃R). Both intracellular Ca²⁺-release and SOCE appear to function in neuro-modulatory domains of the flight circuit during development and acute flight. These findings raise exciting new possibilities for the role of SOCE in vertebrate motor circuit function and the treatment of neurodegenerative disorders where intracellular Ca²⁺ signaling has been implicated as causative.