MEC-2 is recruited to the putative mechanosensory complex in C. elegans touch receptor neurons through its stomatin-like domain.
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.
Zhang
Shifang
S
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Arnadottir
Johanna
J
Keller
Charles
C
Caldwell
Guy A
GA
Yao
C Andrea
CA
Chalfie
Martin
M
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*
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