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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 Youn; Kim, Cha Yeon; Kim, Doyoun; Ko, Jaewon; Um, Ji Won; Lee, Sung Bae; Buck, Matthias; Kim, Eunjoon; Heo, Won Do; Lee, Jie-Oh; Kim, Ho Min
- DGIST Authors
- Ko, Jaewon; Um, Ji Won; Lee, Sung Bae
- Issue Date
- Frontiers in Molecular Neuroscience, 10
- Article Type
- Architecture; Complex; Crystal Structure; Dependent Transsynaptic Adhesion; Heparan Sulfate; Higher-Order Clustering; LAR-RPTPs; Midline Axon Guidance; Molecule; Postsynaptic Ligand; Protein-Tyrosine-Phosphatases; Proteoglycans; Ptp-Sigma; Receptor; Structural Basis; Synaptic 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
Laboratory of Synapse Formation and Function
Synapse Formation and Function; Neural Circuits; 뇌질환; animal model
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Department of Brain and Cognitive SciencesUm Laboratory1. Journal Articles
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