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LAR-RPTP Clustering Is Modulated by Competitive Binding between Synaptic Adhesion Partners and Heparan Sulfate

LAR-RPTP Clustering Is Modulated by Competitive Binding between Synaptic Adhesion Partners and Heparan Sulfate
Won, Seoung YounKim, Cha YeonKim, DoyounKo, JaewonUm, Ji WonLee, Sung BaeBuck, MatthiasKim, EunjoonHeo, Won DoLee, Jie-OhKim, Ho Min
DGIST Authors
Ko, JaewonUm, Ji WonLee, Sung Bae
Issue Date
Frontiers in Molecular Neuroscience, 10
Article Type
ArchitectureComplexCrystal StructureDependent Transsynaptic AdhesionHeparan SulfateHigher-Order ClusteringLAR-RPTPsMidline Axon GuidanceMoleculePostsynaptic LigandProtein-Tyrosine-PhosphatasesProteoglycansPtp-SigmaReceptorStructural BasisSynaptic Adhesion Molecules
The leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) are cellular receptors of heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans that direct axonal growth and neuronal regeneration. LAR-RPTPs are also synaptic adhesion molecules that form trans-synaptic adhesion complexes by binding to various postsynaptic adhesion ligands, such as Slit- and Trk-like family of proteins (Slitrks), IL-1 receptor accessory protein-like 1 (IL1RAPL1), interleukin-1 receptor accessory protein (IL-1RAcP) and neurotrophin receptor tyrosine kinase C (TrkC), to regulate synaptogenesis. Here, we determined the crystal structure of the human LAR-RPTP/IL1RAPL1 complex and found that lateral interactions between neighboring LAR-RPTP/IL1RAPL1 complexes in crystal lattices are critical for the higher-order assembly and synaptogenic activity of these complexes. Moreover, we found that LAR-RPTP binding to the postsynaptic adhesion ligands, Slitrk3, IL1RAPL1 and IL-1RAcP, but not TrkC, induces reciprocal higher-order clustering of trans-synaptic adhesion complexes. Although LAR-RPTP clustering was induced by either HS or postsynaptic adhesion ligands, the dominant binding of HS to the LAR-RPTP was capable of dismantling pre-established LAR-RPTP-mediated trans-synaptic adhesion complexes. These findings collectively suggest that LAR-RPTP clustering for synaptogenesis is modulated by a complex synapse-organizing protein network. © 2017 Won, Kim, Kim, Ko, Um, Lee, Buck, Kim, Heo, Lee and Kim.
Frontiers Media S.A.
Related Researcher
  • Author Lee, Sung Bae Laboratory of Neurodegenerative Diseases and Aging
  • Research Interests Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
Department of Brain and Cognitive SciencesLaboratory of Neurodegenerative Diseases and Aging1. Journal Articles
Department of Brain and Cognitive SciencesSynapse Disorder Laboratory1. Journal Articles

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