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Article

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

1
Department of Biology, Animal Physiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany
2
Department of Ophthalmology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
3
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
4
Department of Computational Biology, University of Lausanne, 1015 Lausanne, Switzerland
*
Author to whom correspondence should be addressed.
Current address: Lehrstuhl für funktionelle und klinische Anatomie, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Current address: Augenklinik, Städtisches Klinikum Karlsruhe, 76133 Karlsruhe, Germany.
§
Current address: Novartis Pharma GmbH, 90429 Nürnberg, Germany.
Int. J. Mol. Sci. 2020, 21(21), 7848; https://doi.org/10.3390/ijms21217848
Received: 28 September 2020 / Revised: 19 October 2020 / Accepted: 20 October 2020 / Published: 22 October 2020
(This article belongs to the Special Issue Molecular Structure and Function of Synapses)
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. View Full-Text
Keywords: Munc13-1; ubMunc13-2; brMunc13-2; Munc13-3; ribbon synapse; conventional synapse; retina; type 6 ON bipolar cell Munc13-1; ubMunc13-2; brMunc13-2; Munc13-3; ribbon synapse; conventional synapse; retina; type 6 ON bipolar cell
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MDPI and ACS Style

Gierke, K.; von Wittgenstein, J.; Hemmerlein, M.; Atorf, J.; Joachimsthaler, A.; Kremers, J.; Cooper, B.H.; Varoqueaux, F.; Regus-Leidig, H.; Brandstätter, J.H. 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. Int. J. Mol. Sci. 2020, 21, 7848. https://doi.org/10.3390/ijms21217848

AMA Style

Gierke K, von Wittgenstein J, Hemmerlein M, Atorf J, Joachimsthaler A, Kremers J, Cooper BH, Varoqueaux F, Regus-Leidig H, Brandstätter JH. 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. International Journal of Molecular Sciences. 2020; 21(21):7848. https://doi.org/10.3390/ijms21217848

Chicago/Turabian Style

Gierke, Kaspar, Julia von Wittgenstein, Maike Hemmerlein, Jenny Atorf, Anneka Joachimsthaler, Jan Kremers, Benjamin H. Cooper, Frederique Varoqueaux, Hanna Regus-Leidig, and Johann H. Brandstätter 2020. "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" International Journal of Molecular Sciences 21, no. 21: 7848. https://doi.org/10.3390/ijms21217848

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