Identification of GPR83 as the receptor for the neuroendocrine peptide PEN

Ivone Gomes, Erin N. Bobeck, Elyssa B. Margolis, Achla Gupta, Salvador Sierra, Amanda K. Fakira, Wakako Fujita, Timo D. Müller, Anne Müller, Matthias H. Tschöp, Gunnar Kleinau, Lloyd D. Fricker, Lakshmi A. Devi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

PEN is an abundant peptide in the brain that has been implicated in the regulation of feeding.We identified a receptor for PEN in mouse hypothalamus and Neuro2A cells. PEN bound to and activated GPR83, a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR). Reduction of GPR83 expression in mouse brain and Neuro2A cells reduced PEN binding and signaling, consistent with GPR83 functioning as the major receptor for PEN. In some brain regions, GPR83 colocalized with GPR171, a GPCR that binds the neuropeptide bigLEN, another neuropeptide that is involved in feeding and is generated from the same precursor protein as is PEN. Coexpression of these two receptors in cell lines altered the signaling properties of each receptor, suggesting a functional interaction. Our data established PEN as a neuropeptide that binds GPR83 and suggested that these two ligand-receptor systems - PEN-GPR83 and bigLEN-GPR171 - may be functionally coupled in the regulation of feeding.

Original languageEnglish (US)
Article numberra43
JournalScience Signaling
Volume9
Issue number425
DOIs
StatePublished - Apr 26 2016

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Peptide Receptors
Brain
Guanine Nucleotides
Neuropeptides
Peptides
Carrier Proteins
Neuropeptide Receptors
Heterotrimeric GTP-Binding Proteins
Protein Precursors
Hypothalamus
Cells
Ligands
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Gomes, I., Bobeck, E. N., Margolis, E. B., Gupta, A., Sierra, S., Fakira, A. K., ... Devi, L. A. (2016). Identification of GPR83 as the receptor for the neuroendocrine peptide PEN. Science Signaling, 9(425), [ra43]. https://doi.org/10.1126/scisignal.aad0694

Identification of GPR83 as the receptor for the neuroendocrine peptide PEN. / Gomes, Ivone; Bobeck, Erin N.; Margolis, Elyssa B.; Gupta, Achla; Sierra, Salvador; Fakira, Amanda K.; Fujita, Wakako; Müller, Timo D.; Müller, Anne; Tschöp, Matthias H.; Kleinau, Gunnar; Fricker, Lloyd D.; Devi, Lakshmi A.

In: Science Signaling, Vol. 9, No. 425, ra43, 26.04.2016.

Research output: Contribution to journalArticle

Gomes, I, Bobeck, EN, Margolis, EB, Gupta, A, Sierra, S, Fakira, AK, Fujita, W, Müller, TD, Müller, A, Tschöp, MH, Kleinau, G, Fricker, LD & Devi, LA 2016, 'Identification of GPR83 as the receptor for the neuroendocrine peptide PEN', Science Signaling, vol. 9, no. 425, ra43. https://doi.org/10.1126/scisignal.aad0694
Gomes I, Bobeck EN, Margolis EB, Gupta A, Sierra S, Fakira AK et al. Identification of GPR83 as the receptor for the neuroendocrine peptide PEN. Science Signaling. 2016 Apr 26;9(425). ra43. https://doi.org/10.1126/scisignal.aad0694
Gomes, Ivone ; Bobeck, Erin N. ; Margolis, Elyssa B. ; Gupta, Achla ; Sierra, Salvador ; Fakira, Amanda K. ; Fujita, Wakako ; Müller, Timo D. ; Müller, Anne ; Tschöp, Matthias H. ; Kleinau, Gunnar ; Fricker, Lloyd D. ; Devi, Lakshmi A. / Identification of GPR83 as the receptor for the neuroendocrine peptide PEN. In: Science Signaling. 2016 ; Vol. 9, No. 425.
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