A single gene encoding two identified splice variants of the InsP3R is found in the genome of the fruit fly Drosophila melanogaster. Mutants that perturb InsP3R function differentially have helped identify systemic processes which require the InsP3R. These include larval feeding, larval molting, fluid transport in malpighian tubules, flight circuit development, and olfactory adaptation. Genetic tools that provide spatiotemporal control on overexpression or knockdown of InsP3R in the whole organism have aided in delineating cellular domains that influence these processes. Genetic interaction studies with InsP3R mutants have helped identify several intracellular signaling components that influence InsP3R function. Measurement of their Ca2+dynamics have further revealed a complex interplay between InsP3R‐mediated Ca2+ release, the endoplasmic reticular Ca2+ pump, and components of store‐operated Ca2+ entry (STIM and Orai). Together these players modulate intracellular Ca2+ signals and homeostasis. Changes in cellular Ca2+ signals brought about by altering levels of the identified intracellular Ca2+ signaling components can be correlated with the extent of changes observed in systemic phenotypes. Furthermore, molecular studies of the Drosophila InsP3R have shown that key functional properties of the InsP3R are evolutionarily conserved. Thus, insights gained from Drosophila are likely to be relevant for our understanding of human disorders caused by aberrant InsP3R‐mediated Ca2+ signaling.
|Journal||Wiley Interdisciplinary Reviews: Membrane Transport and Signaling|
|Publication status||Published - 19 Oct 2011|