LAR-RPTP clustering modulated by competitive binding between synaptic adhesion partners and heparan sulfate = 헤파란 설페이트와 시냅스 후 리간드에 의한 LAR-RPTP 클러스터링 조절 기전 연구

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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 have drawn particular attentions as presynapse organizers orchestrating synaptic connectivity and development. LAR-RPTPs form trans-synaptic adhesion complexes by binding to various postsynaptic adhesion ligands, such as Slitrks, IL1RAPL1, IL-1RAcP, TrkC and SALMs 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.
Advisors
Lee, Jie-Ohresearcher이지오researcherKim, Ho Minresearcher김호민researcher
Description
한국과학기술원 :화학과,
Publisher
한국과학기술원
Issue Date
2018
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 화학과, 2018.8,[iii, 52p :]

Keywords

LAR-RPTPs▼apostsynaptic adhesion partners▼asynaptic adhesion molecules▼aheparan sulfate▼ahigher-order clustering; LAR-RPTPs▼a시냅스 후 리간드▼a시냅스 접착 단백질▼a헤파란 설페이트▼a클러스터링

URI
http://hdl.handle.net/10203/265483
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=828257&flag=dissertation
Appears in Collection
CH-Theses_Ph.D.(박사논문)
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