Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses

Jooyeon Woo, Seok Kyu Kwon, Seungwon Choi, Seho Kim, Jae Ran Lee, Anthone W. Dunah, Morgan Sheng, Eunjoon Kim

Research output: Contribution to journalArticlepeer-review

168 Scopus citations


Synaptic adhesion molecules regulate multiple steps of synapse formation and maturation. The great diversity of neuronal synapses predicts the presence of a large number of adhesion molecules that control synapse formation through trans-synaptic and heterophilic adhesion. We identified a previously unknown trans-synaptic interaction between netrin-G ligand-3 (NGL-3), a postsynaptic density (PSD) 95-interacting postsynaptic adhesion molecule, and leukocyte common antigen-related (LAR), a receptor protein tyrosine phosphatase. NGL-3 and LAR expressed in heterologous cells induced pre- and postsynaptic differentiation in contacting axons and dendrites of cocultured rat hippocampal neurons, respectively. Neuronal overexpression of NGL-3 increased presynaptic contacts on dendrites of transfected neurons. Direct aggregation of NGL-3 on dendrites induced coclustering of excitatory postsynaptic proteins. Knockdown of NGL-3 reduced the number and function of excitatory synapses. Competitive inhibition by soluble LAR reduced NGL-3-induced presynaptic differentiation. These results suggest that the trans-synaptic adhesion between NGL-3 and LAR regulates excitatory synapse formation in a bidirectional manner.

Original languageEnglish (US)
Pages (from-to)428-437
Number of pages10
JournalNature neuroscience
Issue number4
StatePublished - Apr 2009
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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