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.
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DOI：
10.3389/fnmol.2017.00327
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发表时间：
2017
影响因子：
4.8
通讯作者：
Kim HM
中科院分区：
文献类型：
--
作者：
Won SY;Kim CY;Kim D;Ko J;Um JW;Lee SB;Buck M;Kim E;Heo WD;Lee JO;Kim HM
白细胞共同抗原相关受体蛋白酪氨酸磷酸酶（LAR-RPTP）是硫酸乙酰肝素（HS）和硫酸软骨素（CS）蛋白聚糖的细胞受体，其指导轴突生长和神经元再生。LAR-RPTP也是突触粘附分子，其通过与各种突触后粘附配体结合形成跨突触粘附复合物以调节突触发生，所述突触后粘附配体例如Slit-和Trk-样蛋白家族（Slitrks）、IL-1受体辅助蛋白样1（IL-1 RAPL 1）、白细胞介素-1受体辅助蛋白（IL-1 RAcP）和神经营养因子受体酪氨酸激酶C（TrkC）。在这里，我们确定了人类LAR-RPTP/IL 1 RAPL 1复合物的晶体结构，并发现晶格中相邻LAR-RPTP/IL 1 RAPL 1复合物之间的横向相互作用对于这些复合物的高阶组装和突触发生活性至关重要。此外，我们发现，LAR-RPTP结合突触后粘附配体，Slitrk 3，IL-1 RAPL 1和IL-1 RAcP，但不是TrkC，诱导相互高阶聚类的跨突触粘附复合物。虽然LAR-RPTP集群诱导的HS或突触后粘附配体，占主导地位的HS的LAR-RPTP的结合能够拆除预先建立的LAR-RPTP介导的跨突触粘附复合物。这些发现共同表明，LAR-RPTP集群突触是由一个复杂的突触组织蛋白网络调制。
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.
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影响因子：
4.6
作者：
Choi Y;Nam J;Whitcomb DJ;Song YS;Kim D;Jeon S;Um JW;Lee SG;Woo J;Kwon SK;Li Y;Mah W;Kim HM;Ko J;Cho K;Kim E
通讯作者：
Kim E
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
Khan, JA;Brint, EK;Tong, L
通讯作者：
Tong, L
影响因子：
64.8
作者：
Park, Beom Seok;Song, Dong Hyun;Lee, Jie-Oh
通讯作者：
Lee, Jie-Oh
影响因子：
5.7
作者：
Harrison, Oliver J.;Jin, Xiangshu;Hong, Soonjin;Bahna, Fabiana;Ahlsen, Goran;Brasch, Julia;Wu, Yinghao;Vendome, Jeremie;Felsovalyi, Klara;Hampton, Cheri M.;Troyanovsky, Regina B.;Ben-Shau, Avinoam;Frank, Joachim;Troyanovsky, Sergey M.;Shapiro, Lawrence;Honig, Barry
通讯作者：
Honig, Barry