Model organisms: new insights into ion channel and transporter function. Stomatin homologues interact in Caenorhabditis elegans.
In C. elegans the protein UNC-1 is a major determinant of anesthetic sensitivity and is a close homologue of the mammalian protein stomatin. In humans stomatin is missing from erythrocyte membranes in the hemolytic disease overhydrated hereditary stomatocytosis, despite an apparently normal stomatin gene. Overhydrated hereditary stomatocytosis is characterized by alteration of the normal transmembrane gradients of sodium and potassium. Stomatin has been shown to interact genetically with sodium channels. It is also postulated that stomatin is important in the organization of lipid rafts. We demonstrate here that antibodies against UNC-1 stain the major nerve tracts of Caenorhabditis elegans, with very intense staining of the nerve ring. We also found that a gene encoding a stomatin-like protein, UNC-24, affects anesthetic sensitivity and is genetically epistatic to unc-1. In the absence of UNC-24, the staining of the nerve ring by anti-UNC-1 is abolished, despite normal transcriptional levels of the unc-1 mRNA. Western blots indicate that UNC-24 probably affects the stability of the UNC-1 protein. UNC-24 may therefore be necessary for the correct placement of UNC-1 in the cell membrane and organization of lipid rafts.
Sedensky
M M
MM
Department of Anesthesiology, University Hospitals and Case Western Reserve University, Cleveland, Ohio 44106, USA.
Siefker
J M
JM
Morgan
P G
PG
D000818:Animals; D030801:Animals, Genetically Modified; D001798:Blood Proteins / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D003433:Crosses, Genetic; D018076:DNA, Complementary; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000502:physiology*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D015801:Helminth Proteins / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
D001798:Blood Proteins; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D015801:Helminth Proteins; D007473:Ion Channels; D008164:Luminescent Proteins; D008565:Membrane Proteins; C036860:STOM protein, human; D015222:Sodium Channels; C113701:Unc-1 protein, C elegans; D049452:Green Fluorescent Proteins