FMRFamide‐like peptides encoded on the <i>flp‐18</i> precursor gene activate two isoforms of the orphan <i>Caenorhabditis elegans</i> G‐protein‐coupled receptor Y58G8A.4 heterologously expressed in mammalian cells

Kubiak, Teresa M.; Larsen, Martha J.; Bowman, J.W.; Geary, Timothy G.; Lowery, David E.

doi:10.1002/bip.20850

Cited by 35 publications

(39 citation statements)

References 29 publications

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“…The FLP-18 neuropeptide activates two different receptors, NPR-4 and NPR-5 that are related to the mammalian neuropeptide-Y receptor (Kubiak et al, 2008; Cohen et al, 2009). The two receptors have non-overlapping expression with NPR-5 being expressed in select sensory neurons including serotonergic ADF (Cohen et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

Kynurenic Acid Is a Nutritional Cue that Enables Behavioral Plasticity

Lemieux

Cunningham

Lin

et al. 2015

Cell

105

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Summary The kynurenine pathway of tryptophan metabolism is involved in the pathogenesis of several brain diseases but its physiological functions remain unclear. We report that kynurenic acid, a metabolite in this pathway, functions as a regulator of food-dependent behavioral plasticity in C. elegans. The experience of fasting in C. elegans alters a variety of behaviors, including feeding rate, when food is encountered post-fast. Levels of neurally produced kynurenic acid are depleted by fasting leading to activation of NMDA-receptor-expressing interneurons and initiation of a neuropeptide-y like signaling axis that promotes elevated feeding through enhanced serotonin release when animals re-encounter food. Upon re-feeding, kynurenic acid levels are eventually replenished ending the elevated feeding period. Since tryptophan is an essential amino acid, these findings suggest that a physiological role of kynurenic acid is in directly linking metabolism to activity of NMDA and serotonergic circuits, which regulate a broad range of behaviors and physiologies.

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Section: Resultsmentioning

confidence: 99%

Kynurenic Acid Is a Nutritional Cue that Enables Behavioral Plasticity

Lemieux

Cunningham

Lin

et al. 2015

Cell

105

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“…Similarly, at the Drosophila NMJ, seven FLPs encoded by the D. melanogaster FMRFamide gene appear to be functionally redundant (Hewes et al 1998). The FLPs encoded by the flp-18 gene in C. elegans likewise appear to be almost completely redundant, having similar effects and similar potencies on two receptors (Kubiak et al 2008). However, there are several genes in C. elegans that encode FLPs, and evidence suggests that the selectivity for different receptors may vary between other FLPs (Mertens et al 2006).…”

Section: Redundant Peptide Modulators?mentioning

confidence: 99%

Related neuropeptides use different balances of unitary mechanisms to modulate the cardiac neuromuscular system in the American lobster,Homarus americanus

Dickinson

Calkins

Stevens

2015

Journal of Neurophysiology

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To produce flexible outputs, neural networks controlling rhythmic motor behaviors can be modulated at multiple levels, including the pattern generator itself, sensory feedback, and the response of the muscle to a given pattern of motor output. We examined the role of two related neuropeptides, GYSDRNYLRFamide (GYS) and SGRNFLRFamide (SGRN), in modulating the neurogenic lobster heartbeat, which is controlled by the cardiac ganglion (CG). When perfused though an isolated whole heart at low concentrations, both peptides elicited increases in contraction amplitude and frequency. At higher concentrations, both peptides continued to elicit increases in contraction amplitude, but GYS caused a decrease in contraction frequency, while SGRN did not alter frequency. To determine the sites at which these peptides induce their effects, we examined the effects of the peptides on the periphery and on the isolated CG. When we removed the CG and stimulated the motor nerve with constant bursts of stimuli, both GYS and SGRN increased contraction amplitude, indicating that each peptide modulates the muscle or the neuromuscular junction. When applied to the isolated CG, neither peptide altered burst frequency at low peptide concentrations; at higher concentrations, SGRN decreased burst frequency, whereas GYS continued to have no effect on frequency. Together, these data suggest that the two peptides elicit some of their effects using different mechanisms; in particular, given the known feedback pathways within this system, the importance of the negative (nitric oxide) relative to the positive (stretch) feedback pathways may differ in the presence of the two peptides. cardiac ganglion; FMRFamide-like peptide; feedback ADAPTIVE RHYTHMIC BEHAVIOR is determined not only by the output of the nervous system, but also by the interactions of the nervous system with the periphery. Output from the nervous system is transformed into movement at the level of the muscles by way of the neuromuscular transform (Brezina et al. 2000a(Brezina et al. , 2000bBrezina and Weiss 2000;Williams et al. 2013); the resulting movements determine the level and nature of feedback from the periphery, which can in turn affect the output of the nervous system. Thus the generation of rhythmic movements is determined by the integration of activity, inputs, and interactions of multiple components of the multilayered neuromuscular system: the central pattern generator (CPG) and motor neurons, the neuromuscular junctions (NMJs) and muscles, and feedback systems.

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“…In this table, only the most active C. elegans FLPs have been included, and fuller lists of peptides that possess activity on these receptors are given in the referenced papers. Interestingly, AF3, AF4 and AF20 are also potent on FLP18R1a and b (Kubiak et al 2008). AF9 (FLP21) also activates these receptors but at high nM concentrations.…”

Section: Nematodesmentioning

confidence: 99%

“…For example, NPR-1/FLP21R when expressed in Xenopus oocytes activates G i /G o proteins with the opening of inward rectifying potassium channels and when expressed in mammalian CHO cells it also activates G i /G o proteins but when expressed in the pharynx of C. elegans it activates Gaq (Rogers et al 2003; Kubiak The data were taken mainly from Li (2005), Li and Kim (2008), Husson et al (2007) and McVeigh et al (2005b) et al 2003a). It is likely that C. elegans ligand-receptor interactions occur best at temperatures in the 20-30°C range and need accessory proteins, which are different from those in mammalian cells (Kubiak et al 2003a;Mertens et al 2006) although FLP18R1a and b are both fully functional at 37°C (Kubiak et al 2008). Recently, it has been proposed that certain FLPs, viz, AF1, AF10 and PF2, may be the putative ligands for the latrophilin-like receptor isolated from Haemonchus contortus (Muhlfeld et al 2009) though these FLPs exhibited low affinities in the lM range.…”

Section: Nematodesmentioning

confidence: 99%

“…FLPs can also activate more than one receptor, for example, FLP-18 peptides activate NPR1/ FLP21R as well as FLP18R1a, FLP18R1b and FLP18R2 and equally receptors can be activated by more than one FLP family, for example, NPR1/FLP21R can be activated by both FLP-21 and FLP-18 (Rogers et al 2003). More than one signalling pathway can also be associated with ligand-receptor interactions, for example, FLP-18 activation of FLP181a and FLP181b involves both G q and to a lesser extent G s (Kubiak et al 2008) while FLP2Ra and b are both linked to the G q pathway (Mertens et al 2005a). …”

Section: Nematodesmentioning

confidence: 99%

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A review of FMRFamide- and RFamide-like peptides in metazoa

2009

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Neuropeptides are a diverse class of signalling molecules that are widely employed as neurotransmitters and neuromodulators in animals, both invertebrate and vertebrate. However, despite their fundamental importance to animal physiology and behaviour, they are much less well understood than the small molecule neurotransmitters. The neuropeptides are classified into families according to similarities in their peptide sequence; and on this basis, the FMRFamide and RFamide-like peptides, first discovered in molluscs, are an example of a family that is conserved throughout the animal phyla. In this review, the literature on these neuropeptides has been consolidated with a particular emphasis on allowing a comparison between data sets in phyla as diverse as coelenterates and mammals. The intention is that this focus on the structure and functional aspects of FMRFamide and RFamide-like neuropeptides will inform understanding of conserved principles and distinct properties of signalling across the animal phyla.

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FMRFamide‐like peptides encoded on the flp‐18 precursor gene activate two isoforms of the orphan Caenorhabditis elegans G‐protein‐coupled receptor Y58G8A.4 heterologously expressed in mammalian cells

Abstract: Two alternatively spliced variants of an orphanCaenorhabditis elegans G-protein-coupled receptors

Cited by 35 publications

References 29 publications

Kynurenic Acid Is a Nutritional Cue that Enables Behavioral Plasticity

Kynurenic Acid Is a Nutritional Cue that Enables Behavioral Plasticity

Related neuropeptides use different balances of unitary mechanisms to modulate the cardiac neuromuscular system in the American lobster,Homarus americanus

A review of FMRFamide- and RFamide-like peptides in metazoa

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