title: MEC-2 is recruited to the putative mechanosensory complex in C. elegans touch receptor neurons through its stomatin-like domain.
abstract: BACKGROUND
  The response to gentle body touch in C. elegans requires a degenerin channel complex containing four proteins (MEC-2, MEC-4, MEC-6, and MEC-10). The central portion of the integral membrane protein MEC-2 contains a stomatin-like region that is highly conserved from bacteria to mammals. The molecular function of this domain in MEC-2, however, is unknown.
  
  
  RESULTS
  Here, we show that MEC-2 colocalizes with the degenerin MEC-4 in regular puncta along touch receptor neuron processes. This punctate localization requires the other channel complex proteins. The stomatin-like region of MEC-2 interacts with the intracellular cytoplasmic portion of MEC-4. Missense mutations in this region that destroy the interaction also disrupt the punctate localization and degenerin-regulating function of MEC-2. Missense mutations outside this region apparently have no effect on the punctate localization but significantly reduce the regulatory effect of MEC-2 on the MEC-4 degenerin channel. A second stomatin-like protein, UNC-24, colocalizes with MEC-2 in vivo and coimmunoprecipitates with MEC-2 and MEC-4 in Xenopus oocytes; unc-24 enhances the touch insensitivity of temperature-sensitive alleles of mec-4 and mec-6.
  
  
  CONCLUSIONS
  Two stomatin homologs, MEC-2 and UNC-24, interact with the MEC-4 degenerin through their stomatin-like regions, which act as protein binding domains. At least in the case of MEC-2, this binding allows its nonstomatin domains to regulate channel activity. Stomatin-like regions in other proteins may serve a similar protein binding function.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Shifang
authors.initials: S
authors.lastname: Zhang
authors.forename: Johanna
authors.initials: J
authors.lastname: Arnadottir
authors.forename: Charles
authors.initials: C
authors.lastname: Keller
authors.forename: Guy A
authors.initials: GA
authors.lastname: Caldwell
authors.forename: C Andrea
authors.initials: CA
authors.lastname: Yao
authors.forename: Martin
authors.initials: M
authors.lastname: Chalfie
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D005982:Glutathione Transferase; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense / Q000235:genetics; D017434:Protein Structure, Tertiary; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000502:physiology; D014110:Touch / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C096705:MEC-2 protein, C elegans; C115871:Mec-4 protein, C elegans; D008565:Membrane Proteins; C099877:Unc-24 protein, C elegans; D049452:Green Fluorescent Proteins; D005982:Glutathione Transferase