Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase δ (PTPδ), and PTPσ via specific domains regulate excitatory synapse formation

Seok Kyu Kwon, Jooyeon Woo, Soo Young Kim, Hyun Kim, Eunjoon Kim

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Synaptic cell adhesion molecules regulate various steps of synapse formation. The trans-synaptic adhesion between postsynaptic NGL-3 (for netrin-G ligand-3) and presynaptic LAR (for leukocyte antigen-related) regulates excitatory synapse formation in a bidirectional manner. However, little is known about the molecular details of the NGL-3-LAR adhesion and whether two additional LAR family proteins, protein-tyrosine phosphatase δ (PTPδ), and PTPσ, also interact with NGL-3 and are involved in synapse formation. We report here that the leucine-rich repeat (LRR) domain of NGL-3, containing nine LRRs, interacts with the first two fibronectin III (FNIII) domains of LAR to induce bidirectional synapse formation. Moreover, Gln-96 in the first LRR motif of NGL-3 is critical for LARbinding and induction of presynaptic differentiation.PTPδ and PTPσ also interact with NGL-3 via their first two FNIII domains. These two interactions promote synapse formation in a different manner; the PTPσ-NGL-3 interaction promotes synapse formation in a bidirectional manner, whereas the PTPδ-NGL-3 interaction instructs only presynaptic differentiation in a unidirectional manner. mRNAs encoding LAR family proteins display overlapping and differential expression patterns in various brain regions. These results suggest that trans-synaptic adhesion between NGL-3 and the three LAR family proteins regulates excitatory synapse formation in shared and distinct neural circuits.

Original languageEnglish
Pages (from-to)13966-13978
Number of pages13
JournalJournal of Biological Chemistry
Volume285
Issue number18
DOIs
Publication statusPublished - 2010 Apr 30

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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