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- Title
LAR-RPTP Clustering Is Modulated by Competitive Binding between Synaptic Adhesion Partners and Heparan Sulfate.
- Authors
Seoung Youn Won; Cha Yeon Kim; Doyoun Kim; Jaewon Ko; Ji Won Um; Sung Bae Lee; Matthias Buck; Eunjoon Kim; Won Do Heo; Jie-Oh Lee; Ho Min Kim
- Abstract
The leukocyte common antigen-related receptor protein tyrosine phosphatases (LARRPTPs) 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 LARRPTP/IL1RAPL1 complex and found that lateral interactions between neighboring LARRPTP/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.
- Subjects
SYNAPTOGENESIS; HEPARAN sulfate; CRYSTAL structure
- Publication
Frontiers in Molecular Neuroscience, 2017, p1
- ISSN
1662-5099
- Publication type
Article
- DOI
10.3389/fnmol.2017.00327