The mechanosensory protein MEC-6 is a subunit of the C-elegans touch-cell degenerin channel
The mechanosensory protein MEC-6 is a subunit of the C-elegans touch-cell degenerin channel
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DOI：
10.1038/nature01205
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发表时间：
2002-12-12
期刊：
影响因子：
64.8
通讯作者：
Chalfie, M
中科院分区：
文献类型：
--
作者：
Chelur, DS;Ernstrom, GG;Chalfie, M
在线虫和哺乳动物中，触摸感受器神经元的机械感觉转导被认为是由DEG/ENaC(变性/上皮钠通道)蛋白介导的。在线虫中，退化基因mec-4和mec-10(分别表示为mec-4(D)和mec-10(D))的功能获得突变会导致触觉细胞(2，3)退化。这种表型完全被第三个基因mec-6的突变所抑制(参考文献3，4)，该基因是触觉敏感所必需的。最后一个基因也是其他退化素(4-8)的功能所必需的。在这里，我们证明了mec-6编码一种单一的跨膜蛋白，与与人类冠心病有关的对氧磷酶有有限的相似性。该基因在肌肉细胞和许多神经元中表达，包括六个触摸感受器神经元。MEC-6使MEC-4(D)/MEC-10(D)产生的阿米洛利敏感钠电流增加近30倍，并与MEC-2(一种调节MEC-4(D)/MEC-10(D)通道活性的胃素样蛋白(10))协同作用，使电流增加200倍。MEC-6在物理上与所有三种通道蛋白相互作用。在体内，MEC-6与MEC-4共定位，是触觉神经元突起点状表达MEC-4所必需的。我们认为MEC-6是退化素通道复合体的一部分，可能介导了触摸细胞的机械转导。
Mechanosensory transduction in touch receptor neurons is believed to be mediated by DEG/ENaC (degenerin/epithelial Na+ channel) proteins in nematodes and mammals(1). In the nematode Caenorhabditis elegans, gain-of-function mutations in the degenerin genes mec-4 and mec-10 (denoted mec-4(d) and mec-10(d), respectively) cause degeneration of the touch cells(2,3). This phenotype is completely suppressed by mutation in a third gene, mec-6 (refs 3, 4), that is needed for touch sensitivity. This last gene is also required for the function of other degenerins(4-8). Here we show that mec-6 encodes a single-pass membrane-spanning protein with limited similarity to paraoxonases, which are implicated in human coronary heart disease(9). This gene is expressed in muscle cells and in many neurons, including the six touch receptor neurons. MEC-6 increases amiloride-sensitive Na+ currents produced by MEC-4(d)/MEC-10(d) by similar to30-fold, and functions synergistically with MEC-2 (a stomatin-like protein(10) that regulates MEC-4(d)/MEC-10(d) channel activity(11)) to increase the currents by 200-fold. MEC-6 physically interacts with all three channel proteins. In vivo, MEC-6 colocalizes with MEC-4, and is required for punctate MEC-4 expression along touch-neuron processes. We propose that MEC-6 is a part of the degenerin channel complex that may mediate mechanotransduction in touch cells.