The cat-1 gene of Caenorhabditis elegans encodes a vesicular monoamine transporter required for specific monoamine-dependent behaviors.
We have identified the Caenorhabditis elegans homolog of the mammalian vesicular monoamine transporters (VMATs); it is 47% identical to human VMAT1 and 49% identical to human VMAT2. C. elegans VMAT is associated with synaptic vesicles in approximately 25 neurons, including all of the cells reported to contain dopamine and serotonin, plus a few others. When C. elegans VMAT is expressed in mammalian cells, it has serotonin and dopamine transport activity; norepinephrine, tyramine, octopamine, and histamine also have high affinity for the transporter. The pharmacological profile of C. elegans VMAT is closer to mammalian VMAT2 than VMAT1. The C. elegans VMAT gene is cat-1; cat-1 knock-outs are totally deficient for VMAT immunostaining and for dopamine-mediated sensory behaviors, yet they are viable and grow relatively well. The cat-1 mutant phenotypes can be rescued by C. elegans VMAT constructs and also (at least partially) by human VMAT1 or VMAT2 transgenes. It therefore appears that the function of amine neurotransmitters can be completely dependent on their loading into synaptic vesicles.
Duerr
J S
JS
Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Frisby
D L
DL
Gaskin
J
J
Duke
A
A
Asermely
K
K
Huddleston
D
D
Eiden
L E
LE
Rand
J B
JB
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D015306:Biogenic Monoamines / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics*; D004298:Dopamine / Q000032:analysis; D017238:Genes, Helminth; D005815:Genetic Code; D006801:Humans; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000737:chemistry; D009479:Neuropeptides; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D013572:Synaptic Vesicles / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D015306:Biogenic Monoamines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493449:SLC18A1 protein, human; C493452:SLC18A2 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D004298:Dopamine