Journal
JOURNAL OF NEUROBIOLOGY
Volume 64, Issue 3, Pages 239-258Publisher
WILEY
DOI: 10.1002/neu.20146
Keywords
Drosophila; dopamine; transporter; vesicle; serotonin
Categories
Funding
- NIDA NIH HHS [DA00481] Funding Source: Medline
- NIDDK NIH HHS [DK60857] Funding Source: Medline
- NIEHS NIH HHS [ES012078] Funding Source: Medline
- NIMH NIH HHS [MH01709] Funding Source: Medline
- NINDS NIH HHS [R01 NS043171, NS043171] Funding Source: Medline
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Vesicular monoamine transporters (VMATs) mediate the transport of dopamine (DA), serotonin (5HT), and other monoamines into secretory vesicles. The regulation of mammalian VMAT and the related vesicular acetylcholine transporter (VAChT) has been proposed to involve membrane trafficking, but the mechanisms remain unclear. To facilitate a genetic analysis of vesicular transporter function and regulation, we have cloned the Drosophila homolog of the vesicular monoamine transporter (dVMAT). We identify two mRNA splice variants (DVMAT-A and B) that differ at their C-terminus, the domain responsible for endocytosis of mammalian VMAT and VAChT. DVMAT-A contains trafficking motifs conserved in mammals but not C. elegans, and internalization assays indicate that the DVMAT-A C-terminus is involved in endocytosis. DVMAT-B contains a divergent C-terminal domain and is less efficiently internalized from the cell surface. Using in vitro transport assays, we show that DVMAT-A recognizes DA, 5HT, octopamine, tyramine, and histamine as substrates, and similar to mammalian VMAT homologs, is inhibited by the drug reserpine and the environmental toxins 2,2,4,5,6-penta-chlorobiphenyl and heptachlor. We have developed a specific antiserum to DVMAT-A, and find that it localizes to dopaminergic and serotonergic neurons as well as octopa-minergic, type 11 terminals at the neuromuscular junction. Surprisingly, DVMAT-A is co-expressed at type 11 terminals with the Drosophila vesicular glutamate transporter. Our data suggest that DVMAT-A functions as a vesicular transporter for DA, 5HT, and octopamine in vivo, and will provide a powerful invertebrate model for the study of transporter trafficking and regulation. (c) 2005 Wiley Periodicals, Inc.
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