Ligand-independent activity of the ghrelin receptor modulates AMPA receptor trafficking and supports memory formation
Sci. Signal.. 2021-02-16; 14(670):
DOI: 10.1126/scisignal.abb1953
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Ribeiro LF(1), Catarino T(2)(3), Carvalho M(2)(4), Cortes L(2)(3), Santos SD(2)(3), Opazo PO(5)(6), Ribeiro LR(7), Oliveiros B(8)(9), Choquet D(5)(6)(10), Esteban JA(11), Peça J(2)(12), Carvalho AL(1)(12).
Author information:
(1)CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504
Coimbra, Portugal. .
(2)CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504
Coimbra, Portugal.
(3)University of Coimbra, IIIUC-Institute for Interdisciplinary Research,
3030-789 Coimbra, Portugal.
(4)MIT-Portugal Bioengineering Systems Doctoral Program, NOVA University of
Lisbon, 1099-85, Lisboa, Portugal.
(5)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France.
(6)CNRS, UMR 5297, 33000 Bordeaux, France.
(7)Functional and Mechanistic Safety, Clinical Pharmacology and Safety Sciences,
R&D AstraZeneca, Cambridge CB2 0SL, UK.
(8)Laboratory of Biostatistics and Medical Informatics (LBIM), Faculty of
Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
(9)Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of
Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
(10)Bordeaux Imaging Center, UMS 3420, CNRS-Bordeaux University, US4 INSERM,
33000 Bordeaux, France.
(11)Department of Molecular Neurobiology, Centro de Biología Molecular « Severo
Ochoa, » Consejo Superior de Investigaciones Científicas (CSIC)/Universidad
Autónoma de Madrid, 28049 Madrid, Spain.
(12)University of Coimbra, Department of Life Sciences, 3000-456 Coimbra,
Portugal.
The biological signals of hunger, satiety, and memory are interconnected. The
role of the hormone ghrelin in regulating feeding and memory makes ghrelin
receptors attractive targets for associated disorders. We investigated the
effects of the high ligand-independent activity of the ghrelin receptor GHS-R1a
on the physiology of excitatory synapses in the hippocampus. Blocking this
activity produced a decrease in the synaptic content of AMPA receptors in
hippocampal neurons and a reduction in GluA1 phosphorylation at Ser845 Reducing
the ligand-independent activity of GHS-R1a increased the surface diffusion of
AMPA receptors and impaired AMPA receptor-dependent synaptic delivery induced by
chemical long-term potentiation. Accordingly, we found that blocking this GHS-R1a
activity impaired spatial and recognition memory in mice. These observations
support a role for the ligand-independent activity of GHS-R1a in regulating AMPA
receptor trafficking under basal conditions and in the context of synaptic
plasticity that underlies learning.
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American
Association for the Advancement of Science. No claim to original U.S. Government
Works.
DOI: 10.1126/scisignal.abb1953
PMID: 33593997