Trans-synaptic Adhesion Between NGL-3 and LAR Regulates the Formation of Excitatory Synapses

Overview

Journal Nat Neurosci

Date 2009 Mar 3

PMID 19252495

Citations 126

Authors

Jooyeon Woo

Seok-Kyu Kwon

Seungwon Choi

Seho Kim

Jae-Ran Lee

Anthone W Dunah

Morgan Sheng

Eunjoon Kim

Affiliations

Soon will be listed here.

Abstract

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.

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