Duerr J S, Frisby D L, Gaskin J, Duke A, Asermely K, Huddleston D, Eiden L E, Rand J B
Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
J Neurosci. 1999 Jan 1;19(1):72-84. doi: 10.1523/JNEUROSCI.19-01-00072.1999.
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.
我们已经鉴定出秀丽隐杆线虫中与哺乳动物囊泡单胺转运体（VMATs）同源的基因；它与人类VMAT1的同源性为47%，与人类VMAT2的同源性为49%。秀丽隐杆线虫VMAT与大约25个神经元中的突触小泡相关，这些神经元包括所有已报道含有多巴胺和5-羟色胺的细胞，以及其他一些细胞。当秀丽隐杆线虫VMAT在哺乳动物细胞中表达时，它具有5-羟色胺和多巴胺转运活性；去甲肾上腺素、酪胺、章鱼胺和组胺对该转运体也有高亲和力。秀丽隐杆线虫VMAT的药理学特性与哺乳动物VMAT2更为接近，而非VMAT1。秀丽隐杆线虫VMAT基因是cat-1；cat-1基因敲除的线虫完全缺乏VMAT免疫染色以及多巴胺介导的感觉行为，但它们仍能存活且生长相对良好。秀丽隐杆线虫VMAT构建体以及（至少部分地）人类VMAT1或VMAT2转基因可以挽救cat-1突变体的表型。因此，胺类神经递质的功能似乎可能完全依赖于它们被装载到突触小泡中。
