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

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.
Mesh Terms:
Analysis of Variance, Animals, Cell Adhesion Molecules, Cell Differentiation, Cells, Cultured, Coculture Techniques, Embryo, Mammalian, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Hippocampus, Humans, Nerve Tissue Proteins, Neurons, Presynaptic Terminals, Rats, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Receptors, Cell Surface, Synapses, Synaptic Transmission, Transfection, Vesicular Inhibitory Amino Acid Transport Proteins
Nat. Neurosci.
Date: Apr. 01, 2009
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