The DEG/ENaC protein MEC-10 regulates the transduction channel complex in Caenorhabditis elegans touch receptor neurons.
The DEG/ENaC protein MEC-10 regulates the transduction channel complex in Caenorhabditis elegans touch receptor neurons.
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DOI：
10.1523/jneurosci.4580-10.2011
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发表时间：
2011-08-31
期刊：
影响因子：
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通讯作者：
Chalfie M
中科院分区：
文献类型：
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作者：
Arnadóttir J;O'Hagan R;Chen Y;Goodman MB;Chalfie M
秀丽隐杆线虫的轻触感觉是由MEC-4/MEC-10通道复合体介导的，该复合体仅在6个触摸受体神经元（trn）中表达。该复合物包含两个成孔亚基MEC-4和MEC-10，以及附属亚基MEC-2、MEC-6和UNC-24。MEC-4对通道功能至关重要，但除了作为孔隙形成亚基的作用外，MEC-10对通道复合体和触摸感觉的功能贡献尚不清楚。我们通过行为分析、trn的体内电生理记录和MEC-10突变亚型的异源表达来解决这个问题。mec-10缺失的动物仅表现出部分触觉丧失和机械感受器电流（MRC）大小的适度减少。相比之下，先前鉴定的5个mec-10等位基因作为隐性功能获得等位基因，导致完全的触觉不敏感。这些等位基因中的每一个都导致MRC大小的显著减少和体内逆转电位的变化。后一项发现表明，这些mec-10突变改变了体内转导通道的离子选择性。所有mec-10突变动物都有适当定位的通道复合物，这表明MRCs的丢失不是由于转导通道的严重定位错误。最后，对异源表达复合物的电生理检查表明突变的MEC-10蛋白可能通过MEC-2影响通道电流。
Gentle touch sensation in Caenorhabditis elegans is mediated by the MEC-4/MEC-10 channel complex, which is expressed exclusively in six touch receptor neurons (TRNs). The complex contains two pore-forming subunits, MEC-4 and MEC-10, as well as the accessory subunits MEC-2, MEC-6 and UNC-24. MEC-4 is essential for channel function, but beyond its role as a pore-forming subunit, the functional contribution of MEC-10 to the channel complex and to touch sensation is unclear. We addressed this question using behavioral assays, in vivo electrophysiological recordings from TRNs, and heterologous expression of mutant MEC-10 isoforms. Animals with a deletion in mec-10 showed only a partial loss of touch sensitivity and a modest decrease in the size of the mechanoreceptor current (MRC). In contrast, five previously identified mec-10 alleles acted as recessive gain-of-function alleles that resulted in complete touch insensitivity. Each of these alleles produced a substantial decrease in MRC size and a shift in the reversal potential in vivo. The latter finding indicates that these mec-10 mutations alter the ionic selectivity of the transduction channel in vivo. All mec-10 mutant animals had properly localized channel complexes, indicating that the loss of MRCs was not due to a dramatic mislocalization of transduction channels. Finally, electrophysiological examination of heterologously expressed complexes suggests that mutant MEC-10 proteins may affect channel current via MEC-2.