Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK.
Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK.
J Insect Physiol. 2020 Nov-Dec;127:104116. doi: 10.1016/j.jinsphys.2020.104116. Epub 2020 Sep 28.
The tarantula venom toxin GsMTx4 is the only known specific inhibitor of cation-selective mechanosensitive ion channels (MSCs). Its specificity, potency, and ease of use on isolated tissues and cells have made it a powerful pharmacological tool to identify and probe the physiological function of MSCs. In some contexts, however, it would be desirable to deliver the toxin in a controlled way in vivo. Here we describe a novel tool to allow spatial and temporal control of GsMTx4 delivery in vivo in Drosophila. To test the tool, we targeted MSCs required for mechanical nociception in a specific subset of sensory neurons in intact larvae. Expression of GsMTx4 in these neurons results in robust inhibition of mechanical nociception, demonstrating the toxin is active when expressed in vivo. The tool will be particularly useful to manipulate MSC activity in a spatially and temporally-controlled manner to study their role in development, physiology and behaviour in intact, free moving animals.
狼蛛毒液毒素 GsMTx4 是目前已知的阳离子选择性机械门控离子通道（MSCs）的唯一特异性抑制剂。其特异性、效力和在分离组织和细胞上的易用性使其成为识别和探究 MSCs 生理功能的强大药理学工具。然而，在某些情况下，希望能够以受控的方式在体内输送毒素。在这里，我们描述了一种新的工具，可在体内对果蝇中的 GsMTx4 进行时空控制的输送。为了测试该工具，我们将机械伤害感受所需的 MSCs 靶向到完整幼虫中特定感觉神经元的特定亚群中。这些神经元中 GsMTx4 的表达导致机械伤害感受的强烈抑制，表明该毒素在体内表达时是活跃的。该工具将特别有用，可用于以时空可控的方式操纵 MSC 活性，以研究其在完整、自由活动动物的发育、生理和行为中的作用。
