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Optical Control of Metabotropic Glutamate Receptors
G-protein coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype-specificity, spatial p...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681425/ https://www.ncbi.nlm.nih.gov/pubmed/23455609 http://dx.doi.org/10.1038/nn.3346 |
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author | Levitz, Joshua Pantoja, Carlos Gaub, Benjamin Janovjak, Harald Reiner, Andreas Hoagland, Adam Schoppik, David Kane, Brian Stawski, Philipp Schier, Alexander F. Trauner, Dirk Isacoff, Ehud Y. |
author_facet | Levitz, Joshua Pantoja, Carlos Gaub, Benjamin Janovjak, Harald Reiner, Andreas Hoagland, Adam Schoppik, David Kane, Brian Stawski, Philipp Schier, Alexander F. Trauner, Dirk Isacoff, Ehud Y. |
author_sort | Levitz, Joshua |
collection | PubMed |
description | G-protein coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype-specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized “LimGluRs”. The light-agonized “LimGluR2”, on which we focused, is fast, bistable, and supports multiple rounds of on/off switching. Light gates two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. The light-antagonized “LimGluR2block” can be used to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalize the optical control to two additional family members: mGluR3 and 6. The system works in rodent brain slice and in zebrafish in vivo, where we find that mGluR2 modulates the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease. |
format | Online Article Text |
id | pubmed-3681425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-36814252013-10-01 Optical Control of Metabotropic Glutamate Receptors Levitz, Joshua Pantoja, Carlos Gaub, Benjamin Janovjak, Harald Reiner, Andreas Hoagland, Adam Schoppik, David Kane, Brian Stawski, Philipp Schier, Alexander F. Trauner, Dirk Isacoff, Ehud Y. Nat Neurosci Article G-protein coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype-specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized “LimGluRs”. The light-agonized “LimGluR2”, on which we focused, is fast, bistable, and supports multiple rounds of on/off switching. Light gates two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. The light-antagonized “LimGluR2block” can be used to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalize the optical control to two additional family members: mGluR3 and 6. The system works in rodent brain slice and in zebrafish in vivo, where we find that mGluR2 modulates the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease. 2013-03-03 2013-04 /pmc/articles/PMC3681425/ /pubmed/23455609 http://dx.doi.org/10.1038/nn.3346 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Levitz, Joshua Pantoja, Carlos Gaub, Benjamin Janovjak, Harald Reiner, Andreas Hoagland, Adam Schoppik, David Kane, Brian Stawski, Philipp Schier, Alexander F. Trauner, Dirk Isacoff, Ehud Y. Optical Control of Metabotropic Glutamate Receptors |
title | Optical Control of Metabotropic Glutamate Receptors |
title_full | Optical Control of Metabotropic Glutamate Receptors |
title_fullStr | Optical Control of Metabotropic Glutamate Receptors |
title_full_unstemmed | Optical Control of Metabotropic Glutamate Receptors |
title_short | Optical Control of Metabotropic Glutamate Receptors |
title_sort | optical control of metabotropic glutamate receptors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681425/ https://www.ncbi.nlm.nih.gov/pubmed/23455609 http://dx.doi.org/10.1038/nn.3346 |
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