The Caenorhabditis elegans D2-like dopamine receptor DOP-2 physically interacts with GPA-14, a Gαi subunit

The vertebrate dopaminergic system controls a wide variety of physiological and neural functions such as locomotor activity, cognition, emotion, positive reinforcement, food intake, and endocrinal regulation. Aberrations in the levels of dopamine are associated with various disorders such as Parkinson's disease, schizophrenia, hypertension and psychosis [1,2]. In the recent past, efforts have been made to understand the role of dopaminergic signaling in invertebrate behavior and other biological activities due to their tractable genetics, evolutionarily conserved pathways and simpler nervous system. In C. elegans there are eight dopaminergic neurons in the hermaphrodite and an additional set of six neurons located in the tail of the male [3]. Dopamine has been found to participate in a wide array of nematode behaviors such as locomotion, food sensation, egg laying, defecation, and learning [4-8]. Dopamine receptors belong to a super-family of seven-transmembrane G-protein-coupled receptors (GPCRs) which are characterized by three intracellular loops (il1-3), three extracellular loops (ol1-3), an extracellular amino-terminus (Nt) and cytoplasmic carboxy-terminus (Ct) tail [9]. Dopamine receptors transduce external stimuli to the inside of the cell through their interaction with heterotrimeric G-proteins consisting of a guanosine nucleotide binding α-subunit, plus β and γ subunits. The G-protein subunits can further interact with downstream proteins to produce specific effector response(s). An impetus to the clinical advancement came from the development of agonists and antagonists of dopamine receptors as new drug targets [10].In the fully sequenced C. elegans genome, four dopamine receptors have been identified. Based on their sequence profiles and pharmacological properties DOP-1 is classified as a D1-like receptor, DOP-2 and DOP-3 are D2-like receptors and DOP-4 is an invertebrate-specific receptor [11,12]. D1-like receptors transduce signals through Gαs-subunits