Specific neurotransmitters, their receptors and ion channels localized to synaptic termini, play important roles in behavior and synaptic plasticity. Dopamine receptors, characterized by seven trans-membrane domains, are known to act through G-protein coupled pathways. In C. elegans, dopamine has been implicated in a variety of behavioral processes, including both non-associative and associative learning. The worm dop-2 gene represents a dopamine auto-receptor expressed in dopaminergic neurons (Suo et al., 2003). D2-like auto-receptors have been proposed to regulate the release of dopamine from the pre-synaptic neurons as well as reuptake by DAT (Williams and Galli, 2006; Voglis and Tavernarakis, 2008). We are interested in interacting partners of dop-2 and are using its gene product as bait in a ubiquitin-based yeast two hybrid screen.
In the process of reverse transcriptase PCR amplification of worm total RNA we serendipitously amplified an additional splice variant of dop-2, besides the 2 variants K09G1.4a and K09G1.4b (Suo et al., 2003). This third full-length mRNA (K09G1.4c, Figure-1) has 27 additional nucleotides at the 3’ end of exon-8 neighboring the exon:intron junction. The additional sequence codes for 9 amino-acids in the large intracellular loop between trans-membrane domains 5 and 6. The resulting motif (GDLPLPMLL) does not display similarity to any known motif through Pfam match. Interestingly, the regional splicing of all three variants including intron-7 and intron-8 is the conserved GC-AT junction sequence, and not GC-AG commonly found in splice variants in worms and humans (Farrer et al., 2002).
Farrer T, Roller AB, Kent WJ, Zahler AM. (2002). Analysis of the role of Caenorhabditis elegans GC-AG introns in regulated splicing. Nucl. Acids Res. 30, 3360-3367.
Suo S, Sasagawa N, Ishiura S. (2003). Cloning and characterization of a Caenorhabditis elegans D2-like dopamine receptor. J. Neurochem. 86, 869-878.
Williams JM, Galli A. (2006). The dopamine transporter: a vigilant border control for psychostimulant action. Handb. Exp. Pharmacol. 175, 215-232.
oglis G, Tavernarakis N. (2008). A synaptic DEG/ENaC ion channel mediates learning in C. elegansby facilitating dopamine signaling. EMBO J. 27, 3288-3299.
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