Super-resolution imaging reveals the nanoscale organization of metabotropic glutamate receptors at presynaptic active zones.

Autor: Siddig S; Institute of Pharmacology and Toxicology and Bio-Imaging Center, University of Würzburg, Würzburg, Germany.; Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan., Aufmkolk S; Department of Biotechnology and Biophysics, Biocenter, University of Würzburg, Würzburg, Germany.; Department of Neurology & Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada.; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Doose S; Department of Biotechnology and Biophysics, Biocenter, University of Würzburg, Würzburg, Germany., Jobin ML; Institute of Pharmacology and Toxicology and Bio-Imaging Center, University of Würzburg, Würzburg, Germany., Werner C; Department of Biotechnology and Biophysics, Biocenter, University of Würzburg, Würzburg, Germany., Sauer M; Department of Biotechnology and Biophysics, Biocenter, University of Würzburg, Würzburg, Germany., Calebiro D; Institute of Pharmacology and Toxicology and Bio-Imaging Center, University of Würzburg, Würzburg, Germany.; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Nottingham and Birmingham, Birmingham, UK.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2020 Apr 15; Vol. 6 (16), pp. eaay7193. Date of Electronic Publication: 2020 Apr 15 (Print Publication: 2020).
DOI: 10.1126/sciadv.aay7193
Abstrakt: G protein-coupled receptors (GPCRs) play a fundamental role in the modulation of synaptic transmission. A pivotal example is provided by the metabotropic glutamate receptor type 4 (mGluR4), which inhibits glutamate release at presynaptic active zones (AZs). However, how GPCRs are organized within AZs to regulate neurotransmission remains largely unknown. Here, we applied two-color super-resolution imaging by direct stochastic optical reconstruction microscopy ( d STORM) to investigate the nanoscale organization of mGluR4 at parallel fiber AZs in the mouse cerebellum. We find an inhomogeneous distribution, with multiple nanodomains inside AZs, each containing, on average, one to two mGluR4 subunits. Within these nanodomains, mGluR4s are often localized in close proximity to voltage-dependent Ca V 2.1 channels and Munc-18-1, which are both essential for neurotransmitter release. These findings provide previously unknown insights into the molecular organization of GPCRs at AZs, suggesting a likely implication of a close association between mGluR4 and the secretory machinery in modulating synaptic transmission.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)
Databáze: MEDLINE
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