title: MEC-10 and MEC-19 Reduce the Neurotoxicity of the MEC-4(d) DEG/ENaC Channel in Caenorhabditis elegans.
abstract: The Caenorhabditis elegans DEG/ENaC proteins MEC-4 and MEC-10 transduce gentle touch in the six touch receptor neurons . Gain-of-function mutations of mec-4 and mec-4(d) result in a hyperactive channel and neurodegeneration in vivo Loss of MEC-6, a putative DEG/ENaC-specific chaperone, and of the similar protein POML-1 suppresses the neurodegeneration caused by a mec-4(d) mutation. We find that mutation of two genes, mec-10 and a new gene mec-19 (previously named C49G9.1), prevents this action of POML-1, allowing the touch receptor neurons to die in poml-1 mec-4(d) animals. The proteins encoded by these genes normally inhibit mec-4(d) neurotoxicity through different mechanisms. MEC-10, a subunit of the mechanosensory transduction channel with MEC-4, inhibits MEC-4(d) activity without affecting MEC-4 expression. In contrast, MEC-19, a membrane protein specific to nematodes, inhibits MEC-4(d) activity and reduces MEC-4 surface expression.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027.
authors.forename: Yushu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720.
authors.forename: Shashank
authors.initials: S
authors.lastname: Bharill
authors.affiliation: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854.
authors.forename: Robert
authors.initials: R
authors.lastname: O'Hagan
authors.affiliation: Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720.
authors.forename: Ehud Y
authors.initials: EY
authors.lastname: Isacoff
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027 mc21@columbia.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Chalfie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D053503:Epithelial Sodium Channels / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009865:Oocytes / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C094927:Deg-1 protein, C elegans; D053503:Epithelial Sodium Channels; C115871:Mec-4 protein, C elegans; D008565:Membrane Proteins; C085942:MEC-10 protein, C elegans
keywords: Caenorhabditis elegans; DEG/ENaC channels; neurodegeneration; physiological suppressors; touch sensitivity