Abstract
The G-protein coupled receptor (GPCR) family is comprised of seven transmembrane domain proteins and play important roles in nerve transmission, locomotion, proliferation and development, sensory perception, metabolism, and neuromodulation. GPCR research has been targeted by drug developers as a consequence of the wide variety of critical physiological functions regulated by this protein family. Neuropeptide GPCRs are the least characterized of the GPCR family as genetic systems to characterize their functions have lagged behind GPCR gene discovery. Drosophila melanogaster and Caenorhabditis elegans are genetic model organisms that have proved useful in characterizing neuropeptide GPCRs. The strength of a genetic approach leads to an appreciation of the behavioral plasticity that can result from subtle alterations in GPCRs or regulatory proteins in the pathways that GPCRs control. Many of these invertebrate neuropeptides, GPCRs, and signaling pathway components serve as models for mammalian counterparts as they have conserved sequences and function. This review provides an overview of the methods to match neuropeptides to their cognate receptor and a state of the art account of neuropeptide GPCRs that have been characterized in D. melanogaster and C. elegans and the behaviors that have been uncovered through genetic manipulation.
Highlights
Animals respond to environmental cues through alteration of neural circuits that modify behavior and metabolism
These include acetylcholine, γ-aminobutyric acid (GABA), the biogenic amines octopamine, tyramine, dopamine, and serotonin (5-hydroxytryptamine) and glutamate (Bargmann, 2006) function in conjunction with neuropeptides that are produced as precursor proteins that are packed with processing enzymes and stored in large dense core vesicles www.frontiersin.org
Very few G-protein coupled receptor (GPCR) have been matched with their respective neuropeptides and much less is known as to how each neuropeptide GPCR functions in neurotransmission or behavior
Summary
Animals respond to environmental cues through alteration of neural circuits that modify behavior and metabolism. Drosophila melanogaster and C. elegans produce and store most classical small molecule neurotransmitters in synaptic vesicles that cluster for release at pre-synaptic sites These include acetylcholine, γ-aminobutyric acid (GABA), the biogenic amines octopamine, tyramine, dopamine, and serotonin (5-hydroxytryptamine) and glutamate (Bargmann, 2006) function in conjunction with neuropeptides that are produced as precursor proteins that are packed with processing enzymes and stored in large dense core vesicles www.frontiersin.org. D. melanogaster has approximately 160 GPCRs (far less than C. elegans with 44 exhibiting characteristics consistent with peptide ligand receptors (Hewes and Taghert, 2001) In both organisms, very few GPCRs have been matched with their respective neuropeptides and much less is known as to how each neuropeptide GPCR functions in neurotransmission or behavior. Given the diversity of GPCR types and varied functions this review focuses on some of the genetic and molecular techniques that have been used to deorphan neuropeptide GPCRs in C. elegans and D. melanogaster and decipher their role in regulating behavior and physiology
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