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

Cited 43 time in webofscience Cited 47 time in scopus
1,980 Viewed 1,642 Downloaded
Title
Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion
Author(s)
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; Eun Joon Kim; Jie-Oh Lee; Jaewon Ko; Ho Min Kim
Publication Date
2014-11
Journal
NATURE COMMUNICATIONS, v.5, no., pp.5423 -
Publisher
NATURE PUBLISHING GROUP
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 structureguided 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.
URI
https://pr.ibs.re.kr/handle/8788114/758
ISSN
2041-1723
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > Journal Papers (저널논문)
Center for Cognition and Sociality(인지 및 사회성 연구단) > Social Neuroscience Group(사회성 뇌과학 그룹) > Journal Papers (저널논문)
Files in This Item:
2014_112.pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

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

Browse