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

Frontiers in Molecular Neuroscience
Seoung Youn WonHo Min Kim

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 disman...Continue Reading

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Citations

Apr 21, 2018·Frontiers in Molecular Neuroscience·Eunkyung LieEunjoon Kim
Sep 29, 2018·Nature Communications·Atsushi YamagataShuya Fukai
Dec 11, 2020·The FEBS Journal·Shuya Fukai, Tomoyuki Yoshida
Feb 21, 2019·Current Opinion in Structural Biology·Atsushi Yamagata, Shuya Fukai

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Methods Mentioned

BETA
affinity purification
gel filtration
confocal microscopy
size-exclusion chromatography
size exclusion chromatography
electron microscopy
gel-filtration

Software Mentioned

COOT
GraphPad
PyMOL ( Molecular Graphics System
ImageJ
Prism5
PHENIX
HKL2000
AL2CO
PHASER
MetaMorph

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