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Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions
Presynaptic metabotropic glutamate receptors (mGluRs) are essential for the control of synaptic transmission. However, how the subsynaptic dynamics of these receptors is controlled and contributes to synaptic signaling remain poorly understood quantitatively. Particularly, since the affinity of indi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635276/ https://www.ncbi.nlm.nih.gov/pubmed/35511883 http://dx.doi.org/10.1091/mbc.E21-10-0484 |
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author | Bodzęta, Anna Berger, Florian MacGillavry, Harold D. |
author_facet | Bodzęta, Anna Berger, Florian MacGillavry, Harold D. |
author_sort | Bodzęta, Anna |
collection | PubMed |
description | Presynaptic metabotropic glutamate receptors (mGluRs) are essential for the control of synaptic transmission. However, how the subsynaptic dynamics of these receptors is controlled and contributes to synaptic signaling remain poorly understood quantitatively. Particularly, since the affinity of individual mGluR subtypes for glutamate differs considerably, the activation of mGluR subtypes critically depends on their precise subsynaptic distribution. Here, using superresolution microscopy and single-molecule tracking, we unravel novel molecular mechanisms that control the nanoscale distribution and mobility of presynaptic mGluRs in hippocampal neurons. We demonstrate that the high-affinity group II receptor mGluR2 localizes diffusely along the axon, and is highly mobile, while the low-affinity group III receptor mGluR7 is stably anchored at the active zone. We demonstrate that intracellular interactions modulate surface diffusion of mGluR2, while immobilization of mGluR7 at the active zone relies on its extracellular domain. Receptor activation or increases in synaptic activity do not alter the surface mobility of presynaptic mGluRs. Finally, computational modeling of presynaptic mGluR activity revealed that this particular nanoscale arrangement directly impacts their ability to modulate neurotransmitter release. Altogether, this study demonstrates that distinct mechanisms control surface mobility of presynaptic mGluRs to contribute differentially to glutamatergic synaptic transmission. |
format | Online Article Text |
id | pubmed-9635276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-96352762022-11-07 Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions Bodzęta, Anna Berger, Florian MacGillavry, Harold D. Mol Biol Cell Articles Presynaptic metabotropic glutamate receptors (mGluRs) are essential for the control of synaptic transmission. However, how the subsynaptic dynamics of these receptors is controlled and contributes to synaptic signaling remain poorly understood quantitatively. Particularly, since the affinity of individual mGluR subtypes for glutamate differs considerably, the activation of mGluR subtypes critically depends on their precise subsynaptic distribution. Here, using superresolution microscopy and single-molecule tracking, we unravel novel molecular mechanisms that control the nanoscale distribution and mobility of presynaptic mGluRs in hippocampal neurons. We demonstrate that the high-affinity group II receptor mGluR2 localizes diffusely along the axon, and is highly mobile, while the low-affinity group III receptor mGluR7 is stably anchored at the active zone. We demonstrate that intracellular interactions modulate surface diffusion of mGluR2, while immobilization of mGluR7 at the active zone relies on its extracellular domain. Receptor activation or increases in synaptic activity do not alter the surface mobility of presynaptic mGluRs. Finally, computational modeling of presynaptic mGluR activity revealed that this particular nanoscale arrangement directly impacts their ability to modulate neurotransmitter release. Altogether, this study demonstrates that distinct mechanisms control surface mobility of presynaptic mGluRs to contribute differentially to glutamatergic synaptic transmission. The American Society for Cell Biology 2022-06-13 /pmc/articles/PMC9635276/ /pubmed/35511883 http://dx.doi.org/10.1091/mbc.E21-10-0484 Text en © 2022 Bodze˛ta et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License. |
spellingShingle | Articles Bodzęta, Anna Berger, Florian MacGillavry, Harold D. Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions |
title | Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions |
title_full | Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions |
title_fullStr | Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions |
title_full_unstemmed | Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions |
title_short | Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions |
title_sort | subsynaptic mobility of presynaptic mglur types is differentially regulated by intra- and extracellular interactions |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635276/ https://www.ncbi.nlm.nih.gov/pubmed/35511883 http://dx.doi.org/10.1091/mbc.E21-10-0484 |
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