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Calsyntenin-3 Interacts With Both α- And β-Neurexins in the Regulation of Excitatory Synaptic Innervation in Specific Schaffer Collateral Pathways

Title
Calsyntenin-3 Interacts With Both α- And β-Neurexins in the Regulation of Excitatory Synaptic Innervation in Specific Schaffer Collateral Pathways
Authors
Kim, HyeonhoKim, DongwookKim, JinhuLee, Hee-YoonPark, DongseokKang, HyeyeonMatsuda, KeikoSterky, Fredrik H.Yuzaki, MichisukeKim, Jin YoungChoi, Se-YoungKo, JaewonUm, Ji Won
DGIST Authors
Ko, JaewonUm, Ji Won
Issue Date
2020-07
Citation
Journal of Biological Chemistry, 295(27), 9244-9262
Type
Article
Article Type
Article
ISSN
0021-9258
Abstract
Calsyntenin-3 (Clstn3) is a postsynaptic adhesion molecule that induces presynaptic differentiation via presynaptic neurexins (Nrxns), but whether Nrxns directly bind to Clstn3 has been a matter of debate. Here, using LC-MS/MS-based protein analysis, confocal microscopy, RNAscope assays, and electrophysiological recordings, we show that β-Nrxns directly interact via their LNS domain with Clstn3 and Clstn3 cadherin domains. Expression of splice site 4 (SS4) insert-positive β-Nrxn variants, but not insert-negative variants, reversed the impaired Clstn3 synaptogenic activity observed in Nrxn-deficient neurons. Consistently, Clstn3 selectively formed complexes with SS4-positive Nrxns in vivo Neuron-specific Clstn3 deletion caused significant reductions in number of excitatory synaptic inputs. Moreover, expression of Clstn3 cadherin domains in CA1 neurons of Clstn3 conditional knockout mice rescued structural deficits in excitatory synapses, especially within the stratum radiatum layer. Collectively, our results suggest that Clstn3 links to SS4-positive Nrxns to induce presynaptic differentiation and orchestrate excitatory synapse development in specific hippocampal neural circuits, including Schaffer collateral afferents. © 2020 Kim et al.
URI
http://hdl.handle.net/20.500.11750/12039
DOI
10.1074/jbc.RA120.013077
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Related Researcher
  • Author Ko, Jaewon Laboratory of Synapse Formation and Function
  • Research Interests Synapse Formation and Function; Neural Circuits; 뇌질환; animal model
Files:
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Collection:
Department of Brain and Cognitive SciencesLaboratory of Synapse Formation and Function1. Journal Articles
Department of Brain and Cognitive SciencesSynapse Disorder Laboratory1. Journal Articles


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