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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
Lee, Sung Bae
SB LAB(Lab of Neurodegenerative diseases and Aging)
Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
- Department of Brain and Cognitive SciencesLaboratory of Synapse Formation and Function1. Journal Articles
Department of Brain and Cognitive SciencesUm Laboratory1. Journal Articles
Department of Brain and Cognitive SciencesSB LAB(Lab of Neurodegenerative diseases and Aging)1. Journal Articles
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