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Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice

Munc13 isoforms are constituents of the presynaptic compartment of chemical synapses, where they govern important steps in preparing synaptic vesicles for exocytosis. The role of Munc13-1, -2 and -3 is well documented in brain neurons, but less is known about their function and distribution among th...

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Autores principales: Gierke, Kaspar, von Wittgenstein, Julia, Hemmerlein, Maike, Atorf, Jenny, Joachimsthaler, Anneka, Kremers, Jan, Cooper, Benjamin H., Varoqueaux, Frederique, Regus-Leidig, Hanna, Brandstätter, Johann Helmut
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660176/
https://www.ncbi.nlm.nih.gov/pubmed/33105896
http://dx.doi.org/10.3390/ijms21217848
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author Gierke, Kaspar
von Wittgenstein, Julia
Hemmerlein, Maike
Atorf, Jenny
Joachimsthaler, Anneka
Kremers, Jan
Cooper, Benjamin H.
Varoqueaux, Frederique
Regus-Leidig, Hanna
Brandstätter, Johann Helmut
author_facet Gierke, Kaspar
von Wittgenstein, Julia
Hemmerlein, Maike
Atorf, Jenny
Joachimsthaler, Anneka
Kremers, Jan
Cooper, Benjamin H.
Varoqueaux, Frederique
Regus-Leidig, Hanna
Brandstätter, Johann Helmut
author_sort Gierke, Kaspar
collection PubMed
description Munc13 isoforms are constituents of the presynaptic compartment of chemical synapses, where they govern important steps in preparing synaptic vesicles for exocytosis. The role of Munc13-1, -2 and -3 is well documented in brain neurons, but less is known about their function and distribution among the neurons of the retina and their conventional and ribbon-type chemical synapses. Here, we examined the retinae of Munc13-1-, -2-, and -3-EXFP knock-in (KI) mice with a combination of immunocytochemistry, physiology, and electron microscopy. We show that knock-in of Munc13-EXFP fusion proteins did not affect overall retinal anatomy or synapse structure, but slightly affected synaptic transmission. By labeling Munc13-EXFP KI retinae with specific antibodies against Munc13-1, -2 and -3, we found that unlike in the brain, most retinal synapses seem to operate with a single Munc13 isoform. A surprising exception to this rule was type 6 ON bipolar cells, which expressed two Munc13 isoforms in their synaptic terminals, ubMunc13-2 and Munc13-3. The results of this study provide an important basis for future studies on the contribution of Munc13 isoforms in visual signal processing in the mammalian retina.
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spelling pubmed-76601762020-11-13 Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice Gierke, Kaspar von Wittgenstein, Julia Hemmerlein, Maike Atorf, Jenny Joachimsthaler, Anneka Kremers, Jan Cooper, Benjamin H. Varoqueaux, Frederique Regus-Leidig, Hanna Brandstätter, Johann Helmut Int J Mol Sci Article Munc13 isoforms are constituents of the presynaptic compartment of chemical synapses, where they govern important steps in preparing synaptic vesicles for exocytosis. The role of Munc13-1, -2 and -3 is well documented in brain neurons, but less is known about their function and distribution among the neurons of the retina and their conventional and ribbon-type chemical synapses. Here, we examined the retinae of Munc13-1-, -2-, and -3-EXFP knock-in (KI) mice with a combination of immunocytochemistry, physiology, and electron microscopy. We show that knock-in of Munc13-EXFP fusion proteins did not affect overall retinal anatomy or synapse structure, but slightly affected synaptic transmission. By labeling Munc13-EXFP KI retinae with specific antibodies against Munc13-1, -2 and -3, we found that unlike in the brain, most retinal synapses seem to operate with a single Munc13 isoform. A surprising exception to this rule was type 6 ON bipolar cells, which expressed two Munc13 isoforms in their synaptic terminals, ubMunc13-2 and Munc13-3. The results of this study provide an important basis for future studies on the contribution of Munc13 isoforms in visual signal processing in the mammalian retina. MDPI 2020-10-22 /pmc/articles/PMC7660176/ /pubmed/33105896 http://dx.doi.org/10.3390/ijms21217848 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gierke, Kaspar
von Wittgenstein, Julia
Hemmerlein, Maike
Atorf, Jenny
Joachimsthaler, Anneka
Kremers, Jan
Cooper, Benjamin H.
Varoqueaux, Frederique
Regus-Leidig, Hanna
Brandstätter, Johann Helmut
Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice
title Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice
title_full Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice
title_fullStr Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice
title_full_unstemmed Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice
title_short Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice
title_sort heterogeneous presynaptic distribution of munc13 isoforms at retinal synapses and identification of an unconventional bipolar cell type with dual expression of munc13 isoforms: a study using munc13-exfp knock-in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660176/
https://www.ncbi.nlm.nih.gov/pubmed/33105896
http://dx.doi.org/10.3390/ijms21217848
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