Chorna Tetyana, Hasan Gaiti
National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
Biochim Biophys Acta. 2012 Aug;1820(8):1269-82. doi: 10.1016/j.bbagen.2011.11.002. Epub 2011 Nov 7.
Genetic screens for behavioral and physiological defects in Drosophila melanogaster, helped identify several components of calcium signaling of which some, like the Trps, were novel. For genes initially identified in vertebrates, reverse genetic methods have allowed functional studies at the cellular and systemic levels.
The aim of this review is to explain how various genetic methods available in Drosophila have been used to place different arms of Ca2+ signaling in the context of organismal development, physiology and behavior.
Mutants generated in genes encoding a range of Ca2+ transport systems, binding proteins and enzymes affect multiple aspects of neuronal and muscle physiology. Some also affect the maintenance of ionic balance and excretion from malpighian tubules and innate immune responses in macrophages. Aspects of neuronal physiology affected include synaptic growth and plasticity, sensory transduction, flight circuit development and function. Genetic interaction screens have shown that mechanisms of maintaining Ca2+ homeostasis in Drosophila are cell specific and require a synergistic interplay between different intracellular and plasma membrane Ca2+ signaling molecules.
Insights gained through genetic studies of conserved Ca2+ signaling pathways have helped understand multiple aspects of fly physiology. The similarities between mutant phenotypes of Ca2+ signaling genes in Drosophila with certain human disease conditions, especially where homologous genes are causative factors, are likely to aid in the discovery of underlying disease mechanisms and help develop novel therapeutic strategies. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signalling.
对黑腹果蝇行为和生理缺陷进行的遗传筛选,有助于识别钙信号传导的几个组成部分,其中一些,如Trps,是新发现的。对于最初在脊椎动物中鉴定出的基因,反向遗传学方法已可用于细胞和系统水平的功能研究。
本综述的目的是解释果蝇中可用的各种遗传方法是如何被用于将Ca2+信号传导的不同分支置于生物体发育、生理和行为的背景下的。
编码一系列Ca2+转运系统、结合蛋白和酶的基因突变体影响神经元和肌肉生理的多个方面。一些突变体还影响离子平衡的维持以及马氏管的排泄和巨噬细胞中的先天免疫反应。受影响的神经元生理方面包括突触生长和可塑性、感觉转导、飞行回路发育和功能。遗传相互作用筛选表明,果蝇中维持Ca2+稳态的机制具有细胞特异性,并且需要不同细胞内和质膜Ca2+信号分子之间的协同相互作用。
通过对保守的Ca2+信号通路进行遗传研究获得的见解有助于理解果蝇生理的多个方面。果蝇中Ca2+信号基因的突变表型与某些人类疾病状况之间的相似性,特别是在同源基因是致病因素的情况下,可能有助于发现潜在的疾病机制并有助于开发新的治疗策略。本文是名为“细胞内钙信号传导的生化、生物物理和遗传方法”的特刊的一部分。