MEC-10 and MEC-19 Reduce the Neurotoxicity of the MEC-4(d) DEG/ENaC Channel in Caenorhabditis elegans

摘要

The Caenorhabditis elegans DEG/ENaC proteins [MEC-4][1] and [MEC-10][2] transduce gentle touch in the six touch receptor neurons . Gain-of-function mutations of [mec-4][1] and [mec-4][1](d) result in a hyperactive channel and neurodegeneration in vivo . Loss of [MEC-6][3], a putative DEG/ENaC-specific chaperone, and of the similar protein [POML-1][4] suppresses the neurodegeneration caused by a [mec-4][1](d) mutation. We find that mutation of two genes, [mec-10][2] and a new gene [mec-19][5] (previously named [C49G9.1][5]), prevents this action of [POML-1][4], allowing the touch receptor neurons to die in [poml-1][4] [mec-4][1](d) animals. The proteins encoded by these genes normally inhibit [mec-4][1](d) neurotoxicity through different mechanisms. [MEC-10][2], a subunit of the mechanosensory transduction channel with [MEC-4][1], inhibits [MEC-4][1](d) activity without affecting [MEC-4][1] expression. In contrast, [MEC-19][5], a membrane protein specific to nematodes, inhibits [MEC-4][1](d) activity and reduces [MEC-4][1] surface expression. [1]: http://www.wormbase.org/db/get?name=WBGene00003168;class=Gene [2]: http://www.wormbase.org/db/get?name=WBGene00003174;class=Gene [3]: http://www.wormbase.org/db/get?name=WBGene00003170;class=Gene [4]: http://www.wormbase.org/db/get?name=WBGene00010775;class=Gene [5]: http://www.wormbase.org/db/get?name=WBGene00008216;class=Gene