Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion

被引：88

作者：

Um, Ji Won ^{[1
]}

Kim, Kee Hun ^{[2
]}

Park, Beom Seok ^{[3
]}

Choi, Yeonsoo ^{[4
,5
]}

Kim, Doyoun ^{[5
]}

Kim, Cha Yeon ^{[6
]}

Kim, Soo Jin ^{[2
]}

Kim, Minhye ^{[1
]}

Ko, Ji Seung ^{[1
]}

Lee, Seong-Gyu ^{[4
]}

Choii, Gayoung ^{[1
]}

Nam, Jungyong ^{[4
,5
]}

Heo, Won Do ^{[4
,7
]}

Kim, Eunjoon ^{[4
,5
]}

Lee, Jie-Oh ^{[8
]}

Ko, Jaewon ^{[1
,9
]}

Kim, Ho Min ^{[2
]}

机构：

[1] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biochem, Seoul 120749, South Korea

[2] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea

[3] Eulji Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Songnam 461713, South Korea

[4] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea

[5] Inst for Basic Sci Korea, Ctr Synapt Brain Dysfunct, Taejon 305701, South Korea

[6] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Taejon 305701, South Korea

[7] Inst for Basic Sci Korea, Ctr Cognit & Social, Taejon 305701, South Korea

[8] Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea

[9] Yonsei Univ, Coll Med, Dept Psychiat, Seoul 120751, South Korea

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

新加坡国家研究基金会;

关键词：

PROTEIN-TYROSINE-PHOSPHATASES; PTP-SIGMA; NEUREXIN; MOLECULES; DELTA; IMMUNOGLOBULIN; ARCHITECTURE; DOMAINS; NEUROLIGINS; RECOGNITION;

D O I：

10.1038/ncomms6423

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Synaptic adhesion molecules orchestrate synaptogenesis. The presynaptic leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) regulate synapse development by interacting with postsynaptic Slit-and Trk-like family proteins (Slitrks), which harbour two extracellular leucine-rich repeats (LRR1 and LRR2). Here we identify the minimal regions of the LAR-RPTPs and Slitrks, LAR-RPTPs Ig1-3 and Slitrks LRR1, for their interaction and synaptogenic function. Subsequent crystallographic and structure-guided functional analyses reveal that the splicing inserts in LAR-RPTPs are key molecular determinants for Slitrk binding and synapse formation. Moreover, structural comparison of the two Slitrk1 LRRs reveal that unique properties on the concave surface of Slitrk1 LRR1 render its specific binding to LAR-RPTPs. Finally, we demonstrate that lateral interactions between adjacent trans-synaptic LAR-RPTPs/Slitrks complexes observed in crystal lattices are critical for Slitrk1-induced lateral assembly and synaptogenic activity. Thus, we propose a model in which Slitrks mediate synaptogenic functions through direct binding to LAR-RPTPs and the subsequent lateral assembly of LAR-RPTPs/Slitrks complexes.

引用

页数：16

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