1 188

Cited 50 times in

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

Authors
 Ji Won Um  ;  Kee Hun Kim  ;  Beom Seok Park  ;  Yeonsoo Choi  ;  Doyoun Kim  ;  Cha Yeon Kim  ;  Soo Jin Kim  ;  Minhye Kim  ;  Ji Seung Ko  ;  Seong Gyu Lee  ;  Gayoung Choii  ;  Jungyong Nam  ;  Won Do Heo  ;  Eunjoon Kim  ;  Jie Oh Lee  ;  Jaewon Ko  ;  Ho Min Kim 
Citation
 NATURE COMMUNICATIONS, Vol.5 : 5423, 2014 
Journal Title
 NATURE COMMUNICATIONS 
Issue Date
2014
MeSH
Animals ; Binding Sites ; Cell Adhesion/physiology ; HEK293 Cells ; Hippocampus/cytology ; Humans ; Membrane Proteins/metabolism ; Membrane Proteins/physiology* ; Nerve Tissue Proteins/metabolism ; Nerve Tissue Proteins/physiology* ; Protein Structure, Tertiary ; Protein Tyrosine Phosphatases/metabolism ; Protein Tyrosine Phosphatases/physiology* ; Rats ; Real-Time Polymerase Chain Reaction ; Receptor-Like Protein Tyrosine Phosphatases, Class 2/metabolism ; Receptor-Like Protein Tyrosine Phosphatases, Class 2/physiology* ; Repressor Proteins/metabolism ; Repressor Proteins/physiology ; Synapses/metabolism* ; Synapses/physiology
Abstract
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.
Full Text
http://www.nature.com/ncomms/2014/141114/ncomms6423/full/ncomms6423.html
DOI
10.1038/ncomms6423
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Um, Ji Won(엄지원)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/138219
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse