Hodge James J L, Choi James C, O'Kane Cahir J, Griffith Leslie C
Department of Genetics, University of Cambridge, Downing Site, Cambridge CB2 3EH, UK.
J Neurobiol. 2005 Jun;63(3):235-54. doi: 10.1002/neu.20126.
Drosophila Shaw encodes a voltage-insensitive, slowly activating, noninactivating K(+) current. The functional and developmental roles of this channel are unknown. In this study, we use a dominant transgenic strategy to investigate Shaw function and describe a second member of the Shaw family, Shawl. In situ hybridization showed that the two Shaw family genes, Shaw and Shawl, have largely nonoverlapping expression patterns in embryos. Shaw is expressed mainly in excitable cells of the CNS and PNS of late embryos. Shawl is expressed in many nonexcitable cell types: ubiquitously in embryos until the germband extends, then transiently in the developing CNS and PNS, becoming restricted to progressively smaller subsets of the CNS. Ectopic full-length and truncated Shaw localize differently within neurons, and produce uneclosed small pupae and adults with unfurled wings and softened cuticle. This phenotype was mapped to the crustacean cardioactive peptide (CCAP)-neuropeptide circuit. Widespread expression of Shaw in the nervous system results in a reduction in body mass, ether-induced shaking, and lethality. Expression of full-length Shaw had more extreme phenotypic consequences and caused earlier lethality than expression of truncated Shaw in a given GAL4 pattern. Whole cell recordings from ventral ganglion motor neurons expressing the truncated Shaw protein suggest that a major role of Shaw channels in these cells is to contribute to the resting potential.
果蝇的Shaw编码一种对电压不敏感、缓慢激活且不失活的钾离子电流。该通道的功能和发育作用尚不清楚。在本研究中,我们使用显性转基因策略来研究Shaw的功能,并描述了Shaw家族的第二个成员Shawl。原位杂交显示,Shaw和Shawl这两个Shaw家族基因在胚胎中的表达模式基本不重叠。Shaw主要在晚期胚胎中枢神经系统和外周神经系统的可兴奋细胞中表达。Shawl在许多非可兴奋细胞类型中表达:在胚胎中普遍表达,直到胚带延伸,然后在发育中的中枢神经系统和外周神经系统中短暂表达,之后局限于中枢神经系统中逐渐变小的亚群。异位全长和截短的Shaw在神经元内的定位不同,并产生未封闭的小蛹以及翅膀未展开和表皮变软的成虫。这种表型定位于甲壳类心脏活性肽(CCAP)-神经肽回路。Shaw在神经系统中的广泛表达导致体重减轻、乙醚诱导的颤抖和致死性。在给定的GAL4模式下,全长Shaw的表达比截短的Shaw具有更极端的表型后果,并导致更早的致死性。对表达截短Shaw蛋白的腹侧神经节运动神经元进行的全细胞记录表明,Shaw通道在这些细胞中的主要作用是对静息电位有贡献。