Pheromonotropic and melanotropic PK/PBAN receptors: Differential ligand–receptor interactions

Shalev, A. Hariton; Altstein, Miriam

doi:10.1016/j.peptides.2014.10.014

Cited by 11 publications

(8 citation statements)

References 29 publications

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“…Bombyx DH belongs to the PK/ PBAN neuropeptide family that shares the common C-terminal sequence, FXPRL-amide, which also includes PBANs, PVK/PK, and ecdysis-triggering hormone (32). Previous studies have suggested that in ligand-receptor interactions in the FXPRLa neuropeptide family, certain peptides activate their respective cognate receptors with high specificity (32)(33)(34)(35)(36)(37). Bommo-PK has exactly the same C-terminal WFGPRLa motif, but exhibits dramatically decreased functional activities (Fig.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for the interaction of diapause hormone with its receptor in the silkworm, Bombyx mori

et al. 2018

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Diapause hormone (DH) is a 24-aa amidated neuropeptide that elicits the embryonic diapause of the silkworm, Bombyx mori ( Bommo), via sensitive and selective interaction with its receptor, Bommo DH receptor ( Bommo-DHR). Previous studies of the structure-activity relationship of Bommo-DH were all based on an in vivo diapause-induction bioassay, which has provided little information on the structure of Bommo-DHR or its iteration with DH. Here, to unveil the interaction of Bommo-DH with its receptor, N-terminally truncated analogs and alanine-scanning mutants of Bommo-DH were chemically synthesized and functionally evaluated by using a Cy5.5-labeled Bommo-DH competitive binding assay and Bommo-DHR-based functional assays, including cAMP assay and Ca mobilization assay. Our study demonstrates that the C-terminal residues of Arg23 and Leu24 of Bommo-DH are essential for the binding and activation of Bommo-DHR, and that Trp19 and Phe20 also contribute to the functional activity of Bommo-DH. In contrast, when Gly21 or Pro22 were replaced with alanine, both mutants exhibited binding and signaling activities that were indistinguishable from the wild-type peptide. Furthermore, our homology modeling and molecular dynamics simulations, together with experimental validations, have identified the residues of Glu89, Phe172, Phe194, and Tyr299 in Bommo-DHR that are critically involved in the interaction with Bommo-DH. These results may deepen our understanding of the interactions of class-A GPCRs with their peptidic ligands, particularly those between pheromone biosynthesis-activating neuropeptide/DH family neuropeptides and their cognate receptors.-Shen, Z., Jiang, X., Yan, L., Chen, Y., Wang, W., Shi, Y., Shi, L., Liu, D., Zhou, N. Structural basis for the interaction of diapause hormone with its receptor in the silkworm, Bombyx mori.

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Section: Discussionmentioning

confidence: 99%

Structural basis for the interaction of diapause hormone with its receptor in the silkworm, Bombyx mori

et al. 2018

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“…Alternatively, the multiple PBANR transcripts may reflect a spatio-temporal dependence of functionality. This hypothesis is especially attractive given the pleiotropic complexity of PBAN, the multiplicity of reports detailing PBANR activation by multiple FXPRL-amide peptides (Choi et al, 2003;Hariton-Shalev et al, 2013;Kim et al, 2008;Shalev and Altstein, 2015;Watanabe et al, 2007), and the varied tissue/developmental expression profile of PBANR transcripts. In M. brassicae, we detected the mRNA expression of each receptor variant in all life stages.…”

Section: Discussionmentioning

confidence: 99%

Identification and functional characterization of the pheromone biosynthesis activating neuropeptide receptor isoforms from Mamestra brassicae

Fodor

Hull

Köblös

et al. 2018

General and Comparative Endocrinology

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In most moth species, including Mamestra brassicae, pheromone biosynthesis activating neuropeptide (PBAN) regulates pheromone production. Generally, PBAN acts directly on the pheromone gland (PG) cells via its specific G protein-coupled receptor (i.e. PBANR) with Ca as a second messenger. In this study, we identified cDNAs encoding three variants (A, B and C) of the M. brassicae PBANR (Mambr-PBANR). The full-length coding sequences were transiently expressed in cultured Trichoplusia ni cells and Sf9 cells for functional characterization. All three isoforms dose-dependently mobilized extracellular Ca in response to PBAN analogs with Mambr-PBANR-C exhibiting the greatest sensitivity. Fluorescent confocal microscopy imaging studies demonstrated binding of a rhodamine red-labeled ligand (RR10CPBAN) to all three Mambr-PBANR isoforms. RR10CPBAN binding did not trigger ligand-induced internalization in cells expressing PBANR-A, but did in cells expressing the PBANR-B and -C isoforms. Furthermore, activation of the PBANR-B and -C isoforms with the 18 amino acid Mambr-pheromonotropin resulted in co-localization with a Drosophila melanogaster arrestin homolog (Kurtz), whereas stimulation with an unrelated peptide had no effect. PCR-based profiling of the three transcripts revealed a basal level of expression throughout development with a dramatic increase in PG transcripts from the day of adult emergence with PBANR-C being the most abundant.

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“…When expressed in insect Sf9 cells, both receptors responded to femtomolar concentrations of three different species PBAN peptides by increasing intracellular Ca 2+ levels: Pseudaletia separata β‐subesophageal neuropeptide, Locusta migratoria myotropin, and Leucophaea maderae pyrokinin (Shalev & Altstein, ). The synthetic peptide, BBC‐8, activated both receptors to induce Ca 2+ signalling at concentrations as low as 1 aM (Shalev & Altstein, ). Despite the ultra‐potent effect of PBAN peptides, some variants preferentially activated one receptor over the other at ultra‐low concentrations: Ca 2+ responses to Helicoverpa zea PBAN occurred at 100 fM in cells expressing Spl‐PK/PBAN‐R but only in the picomolar range in cells expressing Hep‐PK/PBAN‐R; conversely, cells expressing Hep‐PK/PBAN‐R increased Ca 2+ in response to 1 fM S. littoralis diapause hormone and the synthetic peptide BBC‐5, with no response to any concentration tested in cells expressing Spl‐PK/PBAN‐R (Hariton‐Shalev et al, ; Shalev & Altstein, ).…”

Section: Other Gpcrs Can Generate Ultra‐sensitive Cellular Responsesmentioning

confidence: 99%

“…The synthetic peptide, BBC‐8, activated both receptors to induce Ca 2+ signalling at concentrations as low as 1 aM (Shalev & Altstein, ). Despite the ultra‐potent effect of PBAN peptides, some variants preferentially activated one receptor over the other at ultra‐low concentrations: Ca 2+ responses to Helicoverpa zea PBAN occurred at 100 fM in cells expressing Spl‐PK/PBAN‐R but only in the picomolar range in cells expressing Hep‐PK/PBAN‐R; conversely, cells expressing Hep‐PK/PBAN‐R increased Ca 2+ in response to 1 fM S. littoralis diapause hormone and the synthetic peptide BBC‐5, with no response to any concentration tested in cells expressing Spl‐PK/PBAN‐R (Hariton‐Shalev et al, ; Shalev & Altstein, ). Thus, as was observed for the μ receptors (Sowa et al, ), ultra‐sensitive activation of PK/PBAN receptors is ligand dependent.…”

Section: Other Gpcrs Can Generate Ultra‐sensitive Cellular Responsesmentioning

confidence: 99%

“…They regulate physiological and behavioural functions in order to detect and localise food, to avoid predators and toxins, and to facilitate mating and reproduction (Ha & Smith, 2009 Leucophaea maderae pyrokinin (Shalev & Altstein, 2014). The synthetic peptide, BBC-8, activated both receptors to induce Ca 2+ signalling at concentrations as low as 1 aM (Shalev & Altstein, 2014). environments where the ligand accumulates at a much higher concentration (Vauquelin & Charlton, 2010).…”

Section: Other Gpcrs Can Generate Ultra-sensitive Cellular Responsesmentioning

confidence: 99%

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Signalling in response to sub‐picomolar concentrations of active compounds: Pushing the boundaries of GPCR sensitivity

Civciristov

Halls

2019

British J Pharmacology

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There is evidence for ultra‐sensitive responses to active compounds at concentrations below picomolar levels by proteins and receptors found in species ranging from bacteria to mammals. We have recently shown that such ultra‐sensitivity is also demonstrated by a wide range of prototypical GPCRs, and we have determined the molecular mechanisms behind these responses for three family A GPCRs: the relaxin receptor, RXFP1; the β2‐adrenoceptor; and the M3 muscarinic ACh receptor. Interestingly, there are reports of similar ultra‐sensitivity by more than 15 human GPCR families, in addition to other human receptors and channels. These occur through a diverse range of signalling pathways and produce modulation of important physiological processes, including neuronal transmission, chemotaxis, gene transcription, protein/ion uptake and secretion, muscle contraction and relaxation, and phagocytosis. Here, we summarise the accumulating evidence of ultra‐sensitive receptor signalling to show that this is a common, though currently underappreciated, property of GPCRs. Linked Articles This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

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Pheromonotropic and melanotropic PK/PBAN receptors: Differential ligand–receptor interactions

Cited by 11 publications

References 29 publications

Structural basis for the interaction of diapause hormone with its receptor in the silkworm, Bombyx mori

Structural basis for the interaction of diapause hormone with its receptor in the silkworm, Bombyx mori

Identification and functional characterization of the pheromone biosynthesis activating neuropeptide receptor isoforms from Mamestra brassicae

Signalling in response to sub‐picomolar concentrations of active compounds: Pushing the boundaries of GPCR sensitivity

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