IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-019-13949-x.html
   My bibliography  Save this article

Structural basis of liprin-α-promoted LAR-RPTP clustering for modulation of phosphatase activity

Author

Listed:
  • Xingqiao Xie

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Ling Luo

    (Southern University of Science and Technology)

  • Mingfu Liang

    (Southern University of Science and Technology)

  • Wenchao Zhang

    (Southern University of Science and Technology)

  • Ting Zhang

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Cong Yu

    (Southern University of Science and Technology
    Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, and Shenzhen Key Laboratory of Cell Microenvironment)

  • Zhiyi Wei

    (Southern University of Science and Technology
    Southern University of Science and Technology)

Abstract

Leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) are cell adhesion molecules involved in mediating neuronal development. The binding of LAR-RPTPs to extracellular ligands induces local clustering of LAR-RPTPs to regulate axon growth and synaptogenesis. LAR-RPTPs interact with synaptic liprin-α proteins via the two cytoplasmic phosphatase domains, D1 and D2. Here we solve the crystal structure of LAR_D1D2 in complex with the SAM repeats of liprin-α3, uncovering a conserved two-site binding mode. Cellular analysis shows that liprin-αs robustly promote clustering of LAR in cells by both the liprin-α/LAR interaction and the oligomerization of liprin-α. Structural analysis reveals a unique homophilic interaction of LAR via the catalytically active D1 domains. Disruption of the D1/D1 interaction diminishes the liprin-α-promoted LAR clustering and increases tyrosine dephosphorylation, demonstrating that the phosphatase activity of LAR is negatively regulated by forming clusters. Additionally, we find that the binding of LAR to liprin-α allosterically regulates the liprin-α/liprin-β interaction.

Suggested Citation

  • Xingqiao Xie & Ling Luo & Mingfu Liang & Wenchao Zhang & Ting Zhang & Cong Yu & Zhiyi Wei, 2020. "Structural basis of liprin-α-promoted LAR-RPTP clustering for modulation of phosphatase activity," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13949-x
    DOI: 10.1038/s41467-019-13949-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13949-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13949-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Chikako Nakajima & Masato Sawada & Erika Umeda & Yuma Takagi & Norihiko Nakashima & Kazuya Kuboyama & Naoko Kaneko & Satoaki Yamamoto & Haruno Nakamura & Naoki Shimada & Koichiro Nakamura & Kumiko Mat, 2024. "Identification of the growth cone as a probe and driver of neuronal migration in the injured brain," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13949-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.