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Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions

Title
Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions
Authors
Han, Kyung AhKim, JinhuKim, HyeonhoKim, DongwookLim, DonseokKo, JaewonUm, Ji Won
DGIST Authors
Han, Kyung Ah; Kim, Jinhu; Kim, Hyeonho; Kim, Dongwook; Lim, Donseok; Ko, JaewonUm, Ji Won
Issue Date
2019-11
Citation
Scientific Reports, 9(1), 17094
Type
Article
Article Type
Article
Keywords
ADHESION-LIKE MOLECULESTYROSINE PHOSPHORYLATIONPTP-SIGMAFAMILYCOMPLEXNEUROLIGINSMORPHOGENESISORGANIZATIONNEUREXINDENSITY
ISSN
2045-2322
Abstract
Members of the Slitrk (Slit- and Trk-like protein) family of synaptic cell-adhesion molecules control excitatory and inhibitory synapse development through isoform-dependent extracellular interactions with leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs). However, how Slitrks participate in activation of intracellular signaling pathways in postsynaptic neurons remains largely unknown. Here we report that, among the six members of the Slitrk family, only Slitrk2 directly interacts with the PDZ domain-containing excitatory scaffolds, PSD-95 and Shank3. The interaction of Slitrk2 with PDZ proteins is mediated by the cytoplasmic COOH-terminal PDZ domain-binding motif (Ile-Ser-Glu-Leu), which is not found in other Slitrks. Mapping analyses further revealed that a single PDZ domain of Shank3 is responsible for binding to Slitrk2. Slitrk2 forms in vivo complexes with membrane-associated guanylate kinase (MAGUK) family proteins in addition to PSD-95 and Shank3. Intriguingly, in addition to its role in synaptic targeting in cultured hippocampal neurons, the PDZ domain-binding motif of Slitrk2 is required for Slitrk2 promotion of excitatory synapse formation, transmission, and spine development in the CA1 hippocampal region. Collectively, our data suggest a new molecular mechanism for conferring isoform-specific regulatory actions of the Slitrk family in orchestrating intracellular signal transduction pathways in postsynaptic neurons. © 2019, The Author(s).
URI
http://hdl.handle.net/20.500.11750/10934
DOI
10.1038/s41598-019-53519-1
Publisher
Nature Publishing Group
Related Researcher
  • Author Ko, Jaewon Laboratory of Synapse Formation and Function
  • Research Interests Synapse Formation and Function; Neural Circuits; 뇌질환; animal model
Files:
Collection:
Department of Brain SciencesLaboratory of Synapse Formation and Function1. Journal Articles
Department of Brain SciencesSynapse Disorder Laboratory1. Journal Articles


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