A stomatin and a degenerin interact to control anesthetic sensitivity in Caenorhabditis elegans.
The mechanism of action of volatile anesthetics is unknown. In Caenorhabditis elegans, mutations in the gene unc-1 alter anesthetic sensitivity. The protein UNC-1 is a close homologue of the mammalian protein stomatin. Mammalian stomatin is thought to interact with an as-yet-unknown ion channel to control sodium flux. Using both reporter constructs and translational fusion constructs for UNC-1 and green fluorescent protein (GFP), we have shown that UNC-1 is expressed primarily within the nervous system. The expression pattern of UNC-1 is similar to that of UNC-8, a sodium channel homologue. We examined the interaction of multiple alleles of unc-1 and unc-8 with each other and with other genes affecting anesthetic sensitivity. The data indicate that the protein products of these genes interact, and that an UNC-1/UNC-8 complex is a possible anesthetic target. We propose that membrane-associated protein complexes may represent a general target for volatile anesthetics.
Rajaram
S
S
Departments of Genetics and Anesthesiology, Case Western Reserve University, School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
Spangler
T L
TL
Sedensky
M M
MM
Morgan
P G
PG
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D015801:Helminth Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding
D000777:Anesthetics; D001798:Blood Proteins; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; C094927:Deg-1 protein, C elegans; D015801:Helminth Proteins; D008565:Membrane Proteins