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

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, Shuya Fukai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Article number649
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - 2020/12/01

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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