A Caenorhabditis elegans allatostatin/galanin-like receptor NPR-9 inhibits local search behavior in response to feeding cues

Abstract

Movement inCaenorhabditis elegans is the result of sensory cues creating stimulatory and inhibitory output from sensory neurons. Four interneurons (AIA, AIB, AIY, and AIZ) are the primary recipients of this information that is further processed en route to motor neurons and muscle contraction. C. elegans has >1,000 G proteincoupled receptors (GPCRs), and their contribution to sensory-based movement is largely undefined. We show that an allatostatin/ galanin-like GPCR (NPR-9) is found exclusively in the paired AIB interneuron. AIB interneurons are associated with local search/ pivoting behavior. npr-9 mutants display an increased local search/ pivoting that impairs their ability to roam and travel long distances on food. With impaired roaming behavior on food npr-9 mutants accumulate more intestinal fat as compared with wild type. Overexpression of NPR-9 resulted in a gain-of-function phenotype that exhibits enhanced forward movement with lost pivoting behavior off food. As such the animal travels a great distance off food, creating arcs to return to food. These findings indicate that NPR-9 has inhibitory effects on the AIB interneuron to regulate foraging behavior, which, in turn, may affect metabolic rate and lipid storage.neuropeptide receptor ͉ nerve transmission ͉ foraging ͉ glutamate receptor ͉ interneuron A major challenge in neurobiology is to understand the control of behavior at the molecular level. Neuropeptides and their receptors offer promising candidates for the regulation of various behaviors and changes in physiology. The Caenorhabditis elegans genome sequence has allowed the identification of 109 putative neuropeptide genes encoding precursors that may be processed to Ϸ250 neuropeptides (1-3). These neuropeptides are grouped into three families: FMRFamide-related peptides (f lp), insulin-like peptides (ins), and neuropeptide-like-peptides (nlps). C. elegans expresses Ͼ1,000 orphan G protein-coupled receptors (GPCRs). More than 50 GPCRs resemble known receptors for known neuropeptide families based on phylogenetic comparisons with known vertebrate GPCRs (4). Of these GPCRs, based on sequence identity, C. elegans gene ZK455.3 expresses an nlp receptor, NPR-9, that is most similar to insect allatostatin/ mammalian galanin receptors (5-8). Allatostatins are a family of neuropeptides that share a conserved C-terminal sequence -Tyr/PheXaaPheGlyLeu-NH 2 and are widespread throughout the invertebrate lineage (9, 10). In insects, allatostatins regulate numerous physiological functions, including inhibition of juvenile hormone biosynthesis (11, 12), inhibition of muscle contraction (13), myoendocrine regulation (14, 15), neuromodulation (16), and regulation of enzymatic activities (17) and ecdysis (18). Similarly, mammalian galanin modulates a wide variety of processes that range from neurotransmission, nociception, feeding and metabolism, energy and osmotic homeostasis and learning and memory (19). We report that NPR-9 is uniquely localized in interneuron AIB to negatively regulate a variety of inputs th...

Global view of the evolution and diversity of metazoan neuropeptide signaling

“…The orthology of L11/ CCHamide/EP and neuromedin-B is not recognizable at the pNP level but they are listed as orthologs based on the receptor evidence. Likewise, an orthologous relationship between allatostatin-A and galanin is not evident at the pNP level, but is supported by the orthology of their receptors and a similar role in the regulation of lipid storage (63), among other functions. Neuromedin-B and galanin receptors are present in B. floridae, but no pNP orthologs were found.…”

Allatostatin-A neurons inhibit feeding behavior in adult Drosophila

“…However, as noted earlier, injection of AstA peptide inhibits food intake in a number of other insect species (16). Furthermore, orthologs of AstA receptors have been shown to play a role in feeding in mammals (55)(56)(57) and Caenorhabditis elegans (58). Given these data, it is likely that AstA itself plays a role to promote satiety or aversion to unpalatable food resources in Drosophila, but this remains to be demonstrated.…”

The regulation of feeding and metabolism in response to food deprivation in Caenorhabditis elegans

“…npr-9 mutants showed a lack of roaming behaviour on food, that is, where animals progress in a forward direction which is briefly interrupted by backward movement to change the direction of forward movement. When not on food, npr-9 mutants showed shortened forward movement with high angle turns equivalent to wild-type animals (Bendena et al 2008). npr-9 mutants accumulate fat in their intestines and the gene is only expressed in the AIB interneurons.…”

“…npr-9 mutants accumulate fat in their intestines and the gene is only expressed in the AIB interneurons. Bendena et al (2008) propose that NPR-9 may act antagonistically to GLR-1 (also present on AIB) to regulate foraging. Neuropeptides, including the one which activates NPR-9, may also inhibit release of glutamate (Mellem et al 2002).…”

“…AIAs in turn provide feedback inhibition either directly or indirectly through the release of INS-1. An NPR which has been implicated in local search behaviour is NPR-9, an allatostatin/galanin-like receptor (Bendena et al 2008). npr-9 mutants showed a lack of roaming behaviour on food, that is, where animals progress in a forward direction which is briefly interrupted by backward movement to change the direction of forward movement.…”