Chakraborty Sumita, Hasan Gaiti
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
J Neurogenet. 2012 Sep;26(3-4):328-37. doi: 10.3109/01677063.2012.697501. Epub 2012 Jul 20.
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.
果蝇肌醇 1,4,5 - 三磷酸受体（IP(3)R）与哺乳动物 1 型 IP(3)R 具有 57 - 60%的序列相似性，且彼此共享主要结构域同源性。果蝇单一 IP(3)R 基因 itpr 的突变体以及 Itpr1 基因敲除小鼠均表现出致死性和运动协调缺陷。在此，作者表明大鼠 1 型 IP(3)R（主要的神经元亚型）在果蝇的全神经元区域表达时，在细胞和系统水平上功能性地补充了果蝇 IP(3)R 的功能。它挽救了果蝇 itpr 突变体已确定的神经元表型，包括翅膀姿势、飞行、飞行维持的电生理相关性以及细胞内钙动力学。这是首次在体内证明哺乳动物和果蝇 IP(3)R 之间的功能同源性。这项研究也为果蝇脊髓小脑共济失调的细胞和分子分析铺平了道路，因为已知 SCA15/16 是由人类 ITPR1 的杂合性引起的。
