UNC-1 regulates gap junctions important to locomotion in C. elegans
UNC-1 regulates gap junctions important to locomotion in C. elegans
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DOI：
10.1016/j.cub.2007.06.060
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发表时间：
2007-08-07
期刊：
影响因子：
9.2
通讯作者：
Wang, Zhao-Wen
中科院分区：
文献类型：
--
作者：
Chen, Bojun;Liu, Qiang;Wang, Zhao-Wen
In C.在线虫中，口蛋白样蛋白（SLP）的功能丧失（1f）突变抑制运动[1，2]并调节对挥发性麻醉剂的敏感性[3，4]。unc-1（1f）和unc-9（1f）突变体具有相似表型的原因尚不清楚。我们测试了一个假设，即α-11是α-9形成的间隙连接的调节剂。对体壁肌细胞间连接电流的分析表明，在unc-1（1f）、unc-9（1f）和unc-1（1f）;unc-9（1f）双突变体中，电偶联被抑制的程度相似，这表明UNC-1和UNC-9共同起作用。Punc-1：：DsRED 2和Punc-9：：GFP转录融合体的表达表明unc-1和unc-9在神经元和体壁肌细胞中共表达。免疫组化显示，nc-1和nc-9共定位于细胞间连接处，unc-1（1f）不改变nc-9的表达或亚细胞定位。双分子荧光互补（BiFC）分析表明，在细胞间连接处，α-1和α-9在物理上非常接近。有针对性的拯救实验表明，α-9和β-1主要在神经元中起控制运动的作用。因此，除了最近报道的调节机械敏感离子通道的功能外[5，6]，SLP可能具有调节间隙连接的新功能。
In C. elegans, loss-of-function (1f) mutations of the stomatin-like protein (SLP) UNC-1 and the innexin UNC-9 inhibit locomotion [1, 2] and modulate sensitivity to volatile anesthetics [3, 4]. It was unknown why unc-1(1f) and unc-9(1f) mutants have similar phenotypes. We tested the hypothesis that UNC-11 is a regulator of gap junctions formed by UNC-9. Analyses of junctional currents between body-wall muscle cells showed that electrical coupling was inhibited to a similar degree in unc-1(1f), unc-9(1f), and unc-1(1f);unc-9(1f) double mutants, suggesting that UNC-1 and UNC-9 function together. Expression of Punc-1::DsRED2 and Punc-9::GFP transcriptional fusions suggests that unc-1 and unc-9 are coexpressed in neurons and body-wall muscle cells. Immunohistochemistry showed that UNC-1 and UNC-9 colocalized at intercellular junctions and that unc-1(1f) did not alter UNC-9 expression or subcellular localization. Bimolecular fluorescence complementation (BiFC) assays suggest that UNC-1 and UNC-9 are physically very close at intercellular junctions. Targeted rescue experiments suggest that UNC-9 and UNC-1 function predominantly in neurons to control locomotion. Thus, in addition to the recently reported function of regulating mechanosensitive ion channels [5, 6], SLPs might have a novel function of regulating gap junctions.