Specific Trans-Synaptic Interaction with Inhibitory Interneuronal Neurexin Underlies Differential Ability of Neuroligins to Induce Functional Inhibitory Synapses

Synaptic transmission depends on the matching and alignment of presynaptically released transmitters and postsynaptic neurotransmitter receptors. Neuroligin (NL) and Neurexin (Nrxn) proteins are trans-synaptic adhesion molecules that are important in validation and maturation of specific synapses. N...

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Main Authors: Futai, Kensuke, Doty, Christopher D., Baek, Brian, Ryu, Jubin, Sheng, Morgan Hwa-Tze
Other Authors: Picower Institute for Learning and Memory
Format: Article
Language:en_US
Published: Society for Neuroscience 2013
Online Access:http://hdl.handle.net/1721.1/80785
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author Futai, Kensuke
Doty, Christopher D.
Baek, Brian
Ryu, Jubin
Sheng, Morgan Hwa-Tze
author2 Picower Institute for Learning and Memory
author_facet Picower Institute for Learning and Memory
Futai, Kensuke
Doty, Christopher D.
Baek, Brian
Ryu, Jubin
Sheng, Morgan Hwa-Tze
author_sort Futai, Kensuke
collection MIT
description Synaptic transmission depends on the matching and alignment of presynaptically released transmitters and postsynaptic neurotransmitter receptors. Neuroligin (NL) and Neurexin (Nrxn) proteins are trans-synaptic adhesion molecules that are important in validation and maturation of specific synapses. NL isoforms NL1 and NL2 have specific functional roles in excitatory and inhibitory synapses, respectively, but the molecular basis behind this distinction is still unclear. We show here that the extracellular domain of NL2 confers its unique ability to enhance inhibitory synaptic function when overexpressed in rat hippocampal pyramidal neurons, whereas NL1 normally only promotes excitatory synapses. This specificity is conferred by presynaptic Nrxn isoforms, as NL1 can also induce functional inhibitory synapse connections when the presynaptic interneurons ectopically express an Nrxn isoform that binds to NL1. Our results indicate that trans-synaptic interaction with differentially expressed presynaptic Nrxns underlies the distinct functions of NL1 and NL2, and is sufficient to induce functional inhibitory synapse formation.
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spelling mit-1721.1/807852022-09-26T11:27:02Z Specific Trans-Synaptic Interaction with Inhibitory Interneuronal Neurexin Underlies Differential Ability of Neuroligins to Induce Functional Inhibitory Synapses Futai, Kensuke Doty, Christopher D. Baek, Brian Ryu, Jubin Sheng, Morgan Hwa-Tze Picower Institute for Learning and Memory Futai, Kensuke Baek, Brian Ryu, Jubin Sheng, Morgan Hwa-Tze Synaptic transmission depends on the matching and alignment of presynaptically released transmitters and postsynaptic neurotransmitter receptors. Neuroligin (NL) and Neurexin (Nrxn) proteins are trans-synaptic adhesion molecules that are important in validation and maturation of specific synapses. NL isoforms NL1 and NL2 have specific functional roles in excitatory and inhibitory synapses, respectively, but the molecular basis behind this distinction is still unclear. We show here that the extracellular domain of NL2 confers its unique ability to enhance inhibitory synaptic function when overexpressed in rat hippocampal pyramidal neurons, whereas NL1 normally only promotes excitatory synapses. This specificity is conferred by presynaptic Nrxn isoforms, as NL1 can also induce functional inhibitory synapse connections when the presynaptic interneurons ectopically express an Nrxn isoform that binds to NL1. Our results indicate that trans-synaptic interaction with differentially expressed presynaptic Nrxns underlies the distinct functions of NL1 and NL2, and is sufficient to induce functional inhibitory synapse formation. University of Massachusetts (System) {Start-up Funds) Whitehall Foundation 2013-09-18T13:50:32Z 2013-09-18T13:50:32Z 2013-02 2012-12 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/80785 Futai, K., C. D. Doty, B. Baek, J. Ryu, and M. Sheng. “Specific Trans-Synaptic Interaction with Inhibitory Interneuronal Neurexin Underlies Differential Ability of Neuroligins to Induce Functional Inhibitory Synapses.” Journal of Neuroscience 33, no. 8 (February 20, 2013): 3612-3623. en_US http://dx.doi.org/10.1523/jneurosci.1811-12.2013 Journal of Neuroscience Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Society for Neuroscience Society for Neuroscience
spellingShingle Futai, Kensuke
Doty, Christopher D.
Baek, Brian
Ryu, Jubin
Sheng, Morgan Hwa-Tze
Specific Trans-Synaptic Interaction with Inhibitory Interneuronal Neurexin Underlies Differential Ability of Neuroligins to Induce Functional Inhibitory Synapses
title Specific Trans-Synaptic Interaction with Inhibitory Interneuronal Neurexin Underlies Differential Ability of Neuroligins to Induce Functional Inhibitory Synapses
title_full Specific Trans-Synaptic Interaction with Inhibitory Interneuronal Neurexin Underlies Differential Ability of Neuroligins to Induce Functional Inhibitory Synapses
title_fullStr Specific Trans-Synaptic Interaction with Inhibitory Interneuronal Neurexin Underlies Differential Ability of Neuroligins to Induce Functional Inhibitory Synapses
title_full_unstemmed Specific Trans-Synaptic Interaction with Inhibitory Interneuronal Neurexin Underlies Differential Ability of Neuroligins to Induce Functional Inhibitory Synapses
title_short Specific Trans-Synaptic Interaction with Inhibitory Interneuronal Neurexin Underlies Differential Ability of Neuroligins to Induce Functional Inhibitory Synapses
title_sort specific trans synaptic interaction with inhibitory interneuronal neurexin underlies differential ability of neuroligins to induce functional inhibitory synapses
url http://hdl.handle.net/1721.1/80785
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