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Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease
Trans-regulation of G protein-coupled receptors (GPCRs) by leucine-rich repeat (LRR) transmembrane proteins has emerged as a novel type of synaptic molecular interaction in the last decade. Several studies on LRR–GPCR interactions have revealed their critical role in synapse formation and in establi...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005653/ https://www.ncbi.nlm.nih.gov/pubmed/33790745 http://dx.doi.org/10.3389/fncir.2021.634875 |
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author | Matsunaga, Hayato Aruga, Jun |
author_facet | Matsunaga, Hayato Aruga, Jun |
author_sort | Matsunaga, Hayato |
collection | PubMed |
description | Trans-regulation of G protein-coupled receptors (GPCRs) by leucine-rich repeat (LRR) transmembrane proteins has emerged as a novel type of synaptic molecular interaction in the last decade. Several studies on LRR–GPCR interactions have revealed their critical role in synapse formation and in establishing synaptic properties. Among them, LRR–GPCR interactions between extracellular LRR fibronectin domain-containing family proteins (Elfn1 and Elfn2) and metabotropic glutamate receptors (mGluRs) are particularly interesting as they can affect a broad range of synapses through the modulation of signaling by glutamate, the principal excitatory transmitter in the mammalian central nervous system (CNS). Elfn–mGluR interactions have been investigated in hippocampal, cortical, and retinal synapses. Postsynaptic Elfn1 in the hippocampus and cerebral cortex mediates the tonic regulation of excitatory input onto somatostatin-positive interneurons (INs) through recruitment of presynaptic mGluR7. In the retina, presynaptic Elfn1 binds to mGluR6 and is necessary for synapse formation between rod photoreceptor cells and rod-bipolar cells. The repertoire of binding partners for Elfn1 and Elfn2 includes all group III mGluRs (mGluR4, mGluR6, mGluR7, and mGluR8), and both Elfn1 and Elfn2 can alter mGluR-mediated signaling through trans-interaction. Importantly, both preclinical and clinical studies have provided support for the involvement of the Elfn1–mGluR7 interaction in attention-deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and epilepsy. In fact, Elfn1–mGluR7-associated disorders may reflect the altered function of somatostatin-positive interneuron inhibitory neural circuits, the mesolimbic and nigrostriatal dopaminergic pathway, and habenular circuits, highlighting the need for further investigation into this interaction. |
format | Online Article Text |
id | pubmed-8005653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80056532021-03-30 Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease Matsunaga, Hayato Aruga, Jun Front Neural Circuits Neuroscience Trans-regulation of G protein-coupled receptors (GPCRs) by leucine-rich repeat (LRR) transmembrane proteins has emerged as a novel type of synaptic molecular interaction in the last decade. Several studies on LRR–GPCR interactions have revealed their critical role in synapse formation and in establishing synaptic properties. Among them, LRR–GPCR interactions between extracellular LRR fibronectin domain-containing family proteins (Elfn1 and Elfn2) and metabotropic glutamate receptors (mGluRs) are particularly interesting as they can affect a broad range of synapses through the modulation of signaling by glutamate, the principal excitatory transmitter in the mammalian central nervous system (CNS). Elfn–mGluR interactions have been investigated in hippocampal, cortical, and retinal synapses. Postsynaptic Elfn1 in the hippocampus and cerebral cortex mediates the tonic regulation of excitatory input onto somatostatin-positive interneurons (INs) through recruitment of presynaptic mGluR7. In the retina, presynaptic Elfn1 binds to mGluR6 and is necessary for synapse formation between rod photoreceptor cells and rod-bipolar cells. The repertoire of binding partners for Elfn1 and Elfn2 includes all group III mGluRs (mGluR4, mGluR6, mGluR7, and mGluR8), and both Elfn1 and Elfn2 can alter mGluR-mediated signaling through trans-interaction. Importantly, both preclinical and clinical studies have provided support for the involvement of the Elfn1–mGluR7 interaction in attention-deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and epilepsy. In fact, Elfn1–mGluR7-associated disorders may reflect the altered function of somatostatin-positive interneuron inhibitory neural circuits, the mesolimbic and nigrostriatal dopaminergic pathway, and habenular circuits, highlighting the need for further investigation into this interaction. Frontiers Media S.A. 2021-03-15 /pmc/articles/PMC8005653/ /pubmed/33790745 http://dx.doi.org/10.3389/fncir.2021.634875 Text en Copyright © 2021 Matsunaga and Aruga. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Matsunaga, Hayato Aruga, Jun Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease |
title | Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease |
title_full | Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease |
title_fullStr | Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease |
title_full_unstemmed | Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease |
title_short | Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease |
title_sort | trans-synaptic regulation of metabotropic glutamate receptors by elfn proteins in health and disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005653/ https://www.ncbi.nlm.nih.gov/pubmed/33790745 http://dx.doi.org/10.3389/fncir.2021.634875 |
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