Functional Complementation of Drosophila itpr Mutants by Rat Itpr1

Abstract

Abstract: The Drosophila inositol 1,4,5-trisphosphate receptor (IP₃R) and mammalian type-1 IP₃Rs have 57–60% sequence similarity and share major domain homology with each other. Mutants in the single Drosophila IP₃R gene, itpr, and Itpr1 knockout mice both exhibit lethality and defects in motor coordination. Here the authors show that the rat type-1 IP₃R, which is the major neuronal isoform, when expressed in the pan-neuronal domain in Drosophila, functionally complements Drosophila IP₃R 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 IP₃R. 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::

• calcium homeostasis
• growth
• insect flight
• motor coordination
• SOCE

ACKNOWLEDGEMENTS

We thank Dr. Suzanne Ziegenhorn (NCBS) for generating the UASIP₃R1-CFP construct and transgenics and Ms. Tarjani Agrawal (NCBS) for help with electrophysiological recordings. S.C. is supported by a senior research fellowship (SRF-NET) from the Council of Scientific and Industrial Research, India.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.