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The Journal of Neuroscience, January 1, 1999, 19(1):72-84
The cat-1 Gene of Caenorhabditis elegans Encodes a Vesicular Monoamine Transporter Required for Specific Monoamine-Dependent Behaviors
Janet S. Duerr1, Dennis L. Frisby1, Jennifer Gaskin1, Angie Duke1, Karen Asermely2, David Huddleston2, Lee E. Eiden2, and James B. Rand1 1 Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, and 2 Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892
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 ~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.
Key words: C. elegans; VMAT; vesicular transporter; cat-1; dopamine transport; serotonin transport
Copyright © 1999 Society for Neuroscience 0270-6474/99/19172-13$05.00/0
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