Enhanced locomotion caused by loss of the Drosophila DEG/ENaC protein pickpocket1
Enhanced locomotion caused by loss of the Drosophila DEG/ENaC protein pickpocket1
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DOI：
10.1016/s0960-9822(03)00596-7
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发表时间：
2003-09-02
期刊：
影响因子：
9.2
通讯作者：
Johnson, WA
中科院分区：
文献类型：
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作者：
Ainsley, JA;Pettus, JM;Johnson, WA
节律性运动的协调取决于中枢和外周控制机制之间精确平衡的相互作用。尽管人们对外周本体感觉机械感觉输入知之甚少，但人们认为它为调节节律性运动输出[2]的中枢机制的即时修改提供了有关身体位置的信息。Pickpocket1 （PPK1）是果蝇上皮钠通道（ENaC）家族的一个亚基，在幼虫体壁的多个树突状（md）感觉神经元和上脑[3]的少量双极神经元中表达有限。Ppk1零突变幼虫具有正常的外部触觉和md神经元形态，但在爬行行为上表现出惊人的变化。与野生型相比，PPK1功能的丧失导致爬行速度增加和不寻常的直线路径，停止和转弯次数减少。这种增强的运动是由于持续的蠕动收缩波以更高的频率循环，而收缩周期之间的停顿时间显著减少。突变表型由野生型PPK1转基因拯救，并通过表达ppk1RNAi转基因或显性阴性PPK1亚型进行复制。这些结果表明PPK1通道在控制节律性运动中起着重要作用，并为进一步分析中枢和外周控制机制及其在运动障碍中的作用提供了强大的遗传模型系统。
Coordination of rhythmic locomotion depends upon a precisely balanced interplay between central and peripheral control mechanisms [1]. Although poorly understood, peripheral proprioceptive mechanosensory input is thought to provide information about body position for moment-to-moment modifications of central mechanisms mediating rhythmic motor output [2]. Pickpocket1 (PPK1) is a Drosophila subunit of the epithelial sodium channel (ENaC) family displaying limited expression in multiple dendritic (md) sensory neurons tiling the larval body wall and a small number of bipolar neurons in the upper brain [3]. ppk1 null mutant larvae had normal external touch sensation and md neuron morphology but displayed striking alterations in crawling behavior. Loss of PPK1 function caused an increase in crawling speed and an unusual straight path with decreased stops and turns relative to wild-type. This enhanced locomotion resulted from sustained peristaltic contraction wave cycling at higher frequency with a significant decrease in pause period between contraction cycles. The mutant phenotype was rescued by a wild-type PPK1 transgene and duplicated by expressing a ppk1RNAi transgene or a dominant-negative PPK1 isoform. These results demonstrate that the PPK1 channel plays an essential role in controlling rhythmic locomotion and provide a powerful genetic model system for further analysis of central and peripheral control mechanisms and their role in movement disorders.