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.
Woo
Jooyeon
J
National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea.
Kwon
Seok-Kyu
SK
Choi
Seungwon
S
Kim
Seho
S
Lee
Jae-Ran
JR
Dunah
Anthone W
AW
Sheng
Morgan
M
Kim
Eunjoon
E
D000704:Analysis of Variance; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics; D013569:Synapses / Q000145:classification / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D014162:Transfection / Q000379:methods; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
D015815:Cell Adhesion Molecules; C480698:LRRC4C protein, human; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2