한빛사 논문
KAIST
Abstract
Ji Won Um1,*, Kee Hun Kim2,*, Beom Seok Park3,*, Yeonsoo Choi4,5, Doyoun Kim5, Cha Yeon Kim6, Soo Jin Kim2, Minhye Kim1, Ji Seung Ko1, Seong-Gyu Lee4, Gayoung Choii1, Jungyong Nam4,5, Won Do Heo4,7, Eunjoon Kim4,5, Jie-Oh Lee8, Jaewon Ko1,9 & Ho Min Kim2
1 Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea. 2 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea. 3 Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Seongnam 461-713, Korea. 4 Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea. 5 Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 305-701, Korea. 6 Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea. 7 Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 305-701, Korea. 8 Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea. 9 Department of Psychiatry, Yonsei University College of Medicine, Seoul 120-751, Korea.
* These authors contributed equally to this work.
Correspondence to: Jaewon Ko or Ho Min Kim
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.
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