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Structural insights into selective interaction between type IIa receptor protein tyrosine phosphatases and Liprin-α

Author

Listed:
  • Maiko Wakita

    (The University of Tokyo
    The University of Tokyo
    The University of Tokyo)

  • Atsushi Yamagata

    (The University of Tokyo
    The University of Tokyo
    The University of Tokyo
    CREST, JST)

  • Tomoko Shiroshima

    (The University of Tokyo
    The University of Tokyo
    CREST, JST)

  • Hironori Izumi

    (University of Toyama)

  • Asami Maeda

    (The University of Tokyo
    The University of Tokyo
    CREST, JST)

  • Mizuki Sendo

    (University of Toyama)

  • Ayako Imai

    (University of Toyama)

  • Keiko Kubota

    (The University of Tokyo)

  • Sakurako Goto-Ito

    (The University of Tokyo
    The University of Tokyo
    CREST, JST)

  • Yusuke Sato

    (The University of Tokyo
    The University of Tokyo
    The University of Tokyo
    CREST, JST)

  • Hisashi Mori

    (University of Toyama)

  • Tomoyuki Yoshida

    (University of Toyama
    PRESTO, JST)

  • Shuya Fukai

    (The University of Tokyo
    The University of Tokyo
    The University of Tokyo
    CREST, JST)

Abstract

Synapse formation is induced by transsynaptic interaction of neuronal cell-adhesion molecules termed synaptic organizers. Type IIa receptor protein tyrosine phosphatases (IIa RPTPs) function as presynaptic organizers. The cytoplasmic domain of IIa RPTPs consists of two phosphatase domains, and the membrane-distal one (D2) is essential for synapse formation. Liprin-α, which is an active zone protein critical for synapse formation, interacts with D2 via its C-terminal domain composed of three tandem sterile alpha motifs (tSAM). Structural mechanisms of this critical interaction for synapse formation remain elusive. Here, we report the crystal structure of the complex between mouse PTPδ D2 and Liprin-α3 tSAM at 1.91 Å resolution. PTPδ D2 interacts with the N-terminal helix and the first and second SAMs (SAM1 and SAM2, respectively) of Liprin-α3. Structure-based mutational analyses in vitro and in cellulo demonstrate that the interactions with Liprin-α SAM1 and SAM2 are essential for the binding and synaptogenic activity.

Suggested Citation

  • Maiko Wakita & Atsushi Yamagata & Tomoko Shiroshima & Hironori Izumi & Asami Maeda & Mizuki Sendo & Ayako Imai & Keiko Kubota & Sakurako Goto-Ito & Yusuke Sato & Hisashi Mori & Tomoyuki Yoshida & Shuy, 2020. "Structural insights into selective interaction between type IIa receptor protein tyrosine phosphatases and Liprin-α," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14516-5
    DOI: 10.1038/s41467-020-14516-5
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