LAR-rptp clustering is modulated by competitive binding between synaptic adhesion partners and heparan sulfate

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Title
LAR-rptp clustering is modulated by competitive binding between synaptic adhesion partners and heparan sulfate
Author(s)
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
Publication Date
2017-10
Journal
FRONTIERS IN MOLECULAR NEUROSCIENCE, v.10, no., pp.327 -
Publisher
FRONTIERS MEDIA SA
Abstract
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.
URI
https://pr.ibs.re.kr/handle/8788114/4007
ISSN
1662-5099
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > Journal Papers (저널논문)
Center for Cognition and Sociality(인지 및 사회성 연구단) > Journal Papers (저널논문)
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