Thecat-1Gene ofCaenorhabditis elegansEncodes a Vesicular Monoamine Transporter Required for Specific Monoamine-Dependent Behaviors

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Abstract
We have identified theCaenorhabditis eleganshomolog of the mammalian vesicular monoamine transporters (VMATs); it is 47% identical to human VMAT1 and 49% identical to human VMAT2.C. elegansVMAT is associated with synaptic vesicles in ∼25 neurons, including all of the cells reported to contain dopamine and serotonin, plus a few others. WhenC. elegansVMAT 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 ofC. elegansVMAT is closer to mammalian VMAT2 than VMAT1. TheC. elegansVMAT gene iscat-1;cat-1knock-outs are totally deficient for VMAT immunostaining and for dopamine-mediated sensory behaviors, yet they are viable and grow relatively well. Thecat-1mutant phenotypes can be rescued byC. elegansVMAT 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.