Article abstract
Nature Neuroscience 12, 428 - 437 (2009)
Published online: 1 March 2009 | doi:10.1038/nn.2279
Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses
Jooyeon Woo1,4, Seok-Kyu Kwon1,4, Seungwon Choi1, Seho Kim1, Jae-Ran Lee1, Anthone W Dunah2, Morgan Sheng3 & Eunjoon Kim1
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.
- National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
- MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
- The Picower Institute for Learning and Memory, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
- These authors contributed equally to this work.
Correspondence to: Eunjoon Kim1 e-mail: kime@kaist.ac.kr
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