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Biomolecules
Special Issues
New Insights into Metabotropic Glutamate Receptors
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New Insights into Metabotropic Glutamate Receptors

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 1158

Special Issue Editor

Prof. Dr. Ferdinando Nicoletti

E-Mail Website
Guest Editor
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza Università di Roma, Rome, Italy
Interests: molecular neuropharmacology; cellular and preclinical models of CNS disorders; metabotropic glutamate receptors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabotropic glutamate (mGlu) receptors were discovered 40 years ago (Sladeczek et al., Nature, 1985), and since the cloning of the first mGlu receptor subtype (Masu et al., Nature, 1991), they have attracted the interest of neuroscientists, with an impressive number (>11400) of research and review articles being published. Subtype-selective mGlu receptor ligands (either orthosteric or allosteric ligands) are promising in the treatment of neurological and psychiatric disorders, such as schizophrenia, major depressive disorder, autism spectrum disorder, Parkinson’s disease, stroke, drug addiction, and chronic pain. A few drugs have advanced to phase 2 of clinical development, but none of them have been marketed so far. The clinical genetics of mGlu receptors have also progressed considerably, with variants of GRM3 and GRM7 (the genes encoding the mGlu3 and mGlu7 subtypes) being associated with schizophrenia and developmental delay, respectively. Another aspect of potential clinical interest is the association between autoimmune encephalitis and antibodies directed against mGlu1 and mGlu5 receptors. Although mGlu receptors have been extensively studied in neurons, they are also present in astrocytes, oligodendrocytes, microglia, cells of peripheral organs, immune cells, and stem/progenitor cells. mGlu1 and mGlu3 receptors have been linked to the pathophysiology of malignant melanomas and malignant gliomas, respectively, and mGlu5 receptor blockade holds promise in the treatment of liver disorders. All this will be discussed at the 11th International Meeting on Metabotropic Glutamate Receptors (Taormina, Italy, October 5, 2024) (https://www.mglu.it/) and the Satellite Meeting (September 30, Taormina, Italy, 2024). This Meeting will be the launch platform for this Special Issue (SI), entitled “New Insights into Metabotropic Glutamate Receptors”. This Special Issue aims to incorporate research articles, review articles, position papers, and viewpoints.

Prof. Dr. Ferdinando Nicoletti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabotropic glutamate receptors
  • mGlu receptors
  • psychopharmacology

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Published Papers (1 paper)

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Research

13 pages, 2659 KiB  
Article
Activation of Endoplasmic Reticulum-Localized Metabotropic Glutamate Receptor 5 (mGlu5) Triggers Calcium Release Distinct from Cell Surface Counterparts in Striatal Neurons
by Yuh-Jiin I. Jong, Steven K. Harmon and Karen L. O’Malley
Biomolecules 2025, 15(4), 552; https://doi.org/10.3390/biom15040552 - 9 Apr 2025
Viewed by 866
Abstract
Metabotropic glutamate receptor 5 (mGlu5) plays a fundamental role in synaptic plasticity, potentially serving as a therapeutic target for various neurodevelopmental and psychiatric disorders. Previously, we have shown that mGlu5 can also signal from intracellular membranes in the cortex, hippocampus, [...] Read more.
Metabotropic glutamate receptor 5 (mGlu5) plays a fundamental role in synaptic plasticity, potentially serving as a therapeutic target for various neurodevelopmental and psychiatric disorders. Previously, we have shown that mGlu5 can also signal from intracellular membranes in the cortex, hippocampus, and striatum. Using cytoplasmic Ca2+ indicators, we showed that activated cell surface mGlu5 induced a transient Ca2+ increase, whereas the activation of intracellular mGlu5 mediated a sustained Ca2+ elevation in striatal neurons. Here, we used the newly designed ER-targeted Ca2+ sensor, ER-GCaMP6-150, as a robust, specific approach to directly monitor mGlu5-mediated changes in ER Ca2+ itself. Using this sensor, we found that the activation of cell surface mGlu5 led to small declines in ER Ca2+, whereas the activation of ER-localized mGlu5 resulted in rapid, more pronounced changes. The latter could be blocked by the Gq inhibitor FR9000359, the PLC inhibitor U73122, as well as IP3 and ryanodine receptor blockers. These data demonstrate that like cell surface and nuclear mGlu5, ER-localized receptors play a pivotal role in generating and shaping intracellular Ca2+ signals. Full article
(This article belongs to the Special Issue New Insights into Metabotropic Glutamate Receptors)
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