Fluoxetine-resistant mutants in C. elegans define a novel family of transmembrane proteins.
Fluoxetine (Prozac) is an antidepressant that is thought to act by blocking presynaptic reuptake of the neurotransmitter serotonin. Despite widespread clinical use of fluoxetine, direct evidence for this mechanism has been difficult to obtain in vivo. We have determined that fluoxetine has an additional neuromuscular effect on C. elegans that is distinct from inhibition of serotonin reuptake. By screening for mutants resistant to this effect, we have identified seven genes. We report that two of these genes are homologous to each other and define a novel gene family that encodes over a dozen multipass transmembrane proteins. Our findings may have clinical implications for the mechanism of action of fluoxetine.
Choy
R K
RK
Program in Molecular and Cellular Biology, University of Washington, Seattle 98195, USA.
Thomas
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004351:Drug Resistance; D005473:Fluoxetine / Q000494:pharmacology*; D017238:Genes, Helminth; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D016296:Mutagenesis; D009469:Neuromuscular Junction / Q000187:drug effects; D010802:Phylogeny; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D016415:Sequence Alignment
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C499577:ndg-4 protein, C elegans; C121507:nrf-6 protein, C elegans; D005473:Fluoxetine