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

Author

Listed:
  • Ji Won Um

    (College of Life Science and Biotechnology, Yonsei University)

  • Kee Hun Kim

    (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST))

  • Beom Seok Park

    (College of Health Science, Eulji University)

  • Yeonsoo Choi

    (Korea Advanced Institute of Science and Technology (KAIST)
    Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS))

  • Doyoun Kim

    (Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS))

  • Cha Yeon Kim

    (Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology (KAIST))

  • Soo Jin Kim

    (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST))

  • Minhye Kim

    (College of Life Science and Biotechnology, Yonsei University)

  • Ji Seung Ko

    (College of Life Science and Biotechnology, Yonsei University)

  • Seong-Gyu Lee

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Gayoung Choii

    (College of Life Science and Biotechnology, Yonsei University)

  • Jungyong Nam

    (Korea Advanced Institute of Science and Technology (KAIST)
    Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS))

  • Won Do Heo

    (Korea Advanced Institute of Science and Technology (KAIST)
    Center for Cognition and Sociality, Institute for Basic Science (IBS))

  • Eunjoon Kim

    (Korea Advanced Institute of Science and Technology (KAIST)
    Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS))

  • Jie-Oh Lee

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Jaewon Ko

    (College of Life Science and Biotechnology, Yonsei University
    Yonsei University College of Medicine)

  • Ho Min Kim

    (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST))

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.

Suggested Citation

  • 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 &, 2014. "Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion," Nature Communications, Nature, vol. 5(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6423
    DOI: 10.1038/ncomms6423
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    Cited by:

    1. Christos Gogou & J. Wouter Beugelink & Cátia P. Frias & Leanid Kresik & Natalia Jaroszynska & Uwe Drescher & Bert J. C. Janssen & Robert Hindges & Dimphna H. Meijer, 2024. "Alternative splicing controls teneurin-3 compact dimer formation for neuronal recognition," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Kyung Ah Han & Taek-Han Yoon & Jinhu Kim & Jusung Lee & Ju Yeon Lee & Gyubin Jang & Ji Won Um & Jong Kyoung Kim & Jaewon Ko, 2024. "Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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