@article {477, title = {A genetic RNAi screen for IP$_{3}$/Ca{\texttwosuperior}$^{+}$ coupled GPCRs in Drosophila identifies the PdfR as a regulator of insect flight. [Drosophila facility]}, journal = {PLoS Genet}, volume = {9}, year = {2013}, month = {2013}, pages = {e1003849}, abstract = {

Insect flight is regulated by various sensory inputs and neuromodulatory circuits which function in synchrony to control and fine-tune the final behavioral outcome. The cellular and molecular bases of flight neuromodulatory circuits are not well defined. In Drosophila melanogaster, it is known that neuronal IP3 receptor mediated Ca{\texttwosuperior}$^{+}$ signaling and store-operated Ca{\texttwosuperior}$^{+}$ entry (SOCE) are required for air-puff stimulated adult flight. However, G-protein coupled receptors (GPCRs) that activate intracellular Ca{\texttwosuperior}$^{+}$ signaling in the context of flight are unknown in Drosophila. We performed a genetic RNAi screen to identify GPCRs that regulate flight by activating the IPIP$_{3}$ receptor. Among the 108 GPCRs screened, we discovered 5 IPIP$_{3}$/Ca{\texttwosuperior}$^{+}$ linked GPCRs that are necessary for maintenance of air-puff stimulated flight. Analysis of their temporal requirement established that while some GPCRs are required only during flight circuit development, others are required both in pupal development as well as during adult flight. Interestingly, our study identified the Pigment Dispersing Factor Receptor (PdfR) as a regulator of flight circuit development and as a modulator of acute flight. From the analysis of PdfR expressing neurons relevant for flight and its well-defined roles in other behavioral paradigms, we propose that PdfR signaling functions systemically to integrate multiple sensory inputs and modulate downstream motor behavior.

}, keywords = {Adult, Animals, Calcium Signaling, Drosophila melanogaster, Drosophila Proteins, Flight, Animal, Humans, Inositol 1,4,5-Trisphosphate Receptors, Neurons, Receptors, G-Protein-Coupled, RNA Interference, Signal Transduction}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003849}, author = {Agrawal, Tarjani and Sadaf, Sufia and Hasan, Gaiti} } @article {478, title = {Functional implementation of Drosophila itpr mutants by rat Itpr1. [Drosophila facility]}, journal = {J Neurogenet}, volume = {26}, year = {2012}, month = {2012 Sep}, pages = {328-37}, abstract = {

The Drosophila inositol 1,4,5-trisphosphate receptor (IP(3)R) and mammalian type-1 IP(3)Rs have 57-60\% sequence similarity and share major domain homology with each other. Mutants in the single Drosophila IP(3)R gene, itpr, and Itpr1 knockout mice both exhibit lethality and defects in motor coordination. Here the authors show that the rat type-1 IP(3)R, which is the major neuronal isoform, when expressed in the pan-neuronal domain in Drosophila, functionally complements Drosophila IP(3)R function at cellular and systemic levels. It rescues the established neuronal phenotypes of itpr mutants in Drosophila, including wing posture, flight, electrophysiological correlates of flight maintenance, and intracellular calcium dynamics. This is the first in vivo demonstration of functional homology between a mammalian and fly IP(3)R. This study also paves the way for cellular and molecular analyses of the spinocerebellar ataxias in Drosophila, since SCA15/16 is known to be caused by heterozygosity of human ITPR1.

}, keywords = {Animals, Animals, Genetically Modified, Calcium, Cells, Cultured, Cytosol, Drosophila, Drosophila Proteins, Flight, Animal, Gene Expression Regulation, Genetic Therapy, Inositol 1,4,5-Trisphosphate Receptors, Larva, Movement Disorders, Mutation, Neurons, Physical Stimulation, Rats, Transcription Factors, Wings, Animal}, issn = {1563-5260}, doi = {10.3109/01677063.2012.697501}, author = {Chakraborty, Sumita and Hasan, Gaiti} } @article {483, title = {Inositol 1,4,5-trisphosphate receptor and dSTIM function in Drosophila insulin-producing neurons regulates systemic intracellular calcium homeostasis and flight. [Drosophila facility]}, journal = {J Neurosci}, volume = {30}, year = {2010}, month = {2010 Jan 27}, pages = {1301-13}, 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.

}, keywords = {Animals, Calcium, Calcium Signaling, Cell Membrane, Cells, Cultured, Central Nervous System, Drosophila, Drosophila Proteins, Flight, Animal, Homeostasis, Inositol 1,4,5-Trisphosphate Receptors, Insulin, Intracellular Fluid, Membrane Proteins, Mutation, Neural Pathways, Neurons, Pupa, Stromal Interaction Molecule 1}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3668-09.2010}, author = {Agrawal, Neha and Venkiteswaran, Gayatri and Sadaf, Sufia and Padmanabhan, Nisha and Banerjee, Santanu and Hasan, Gaiti} }