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

doi:10.1038/nn.2279

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 journal › Article › peer-review

168 Scopus citations

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.

Original language	English (US)
Pages (from-to)	428-437
Number of pages	10
Journal	Nature neuroscience
Volume	12
Issue number	4
DOIs	https://doi.org/10.1038/nn.2279
State	Published - Apr 2009
Externally published	Yes

ASJC Scopus subject areas

Neuroscience(all)

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@article{6091bf8a4a374d4ebfe664975f7c16f6,

title = "Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses",

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.",

author = "Jooyeon Woo and Kwon, {Seok Kyu} and Seungwon Choi and Seho Kim and Lee, {Jae Ran} and Dunah, {Anthone W.} and Morgan Sheng and Eunjoon Kim",

note = "Funding Information: We would like to thank A.M. Craig for neurexin 1a, 2a, 3a and 1b cDNAs, T. Biederer for SynCAM 1, Y.-P. Hsueh for Syndecan-2, P. Maness for NCAM-140, J. Ko for quantitative analysis, J. Nam for SALM4, M.-H. Kim for the mini analysis program, and Y.-G. Oh, M.-S. Baek, M. Ryu and J.-G. Jung for the help with antibody generation. This work was supported by the National Creative Research Initiative Program of the Korean Ministry of Science and Technology (E.K.).",

year = "2009",

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doi = "10.1038/nn.2279",

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AU - Woo, Jooyeon

AU - Kwon, Seok Kyu

AU - Choi, Seungwon

AU - Kim, Seho

AU - Lee, Jae Ran

AU - Dunah, Anthone W.

AU - Sheng, Morgan

AU - Kim, Eunjoon

N1 - Funding Information: We would like to thank A.M. Craig for neurexin 1a, 2a, 3a and 1b cDNAs, T. Biederer for SynCAM 1, Y.-P. Hsueh for Syndecan-2, P. Maness for NCAM-140, J. Ko for quantitative analysis, J. Nam for SALM4, M.-H. Kim for the mini analysis program, and Y.-G. Oh, M.-S. Baek, M. Ryu and J.-G. Jung for the help with antibody generation. This work was supported by the National Creative Research Initiative Program of the Korean Ministry of Science and Technology (E.K.).

PY - 2009/4

Y1 - 2009/4

N2 - 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.

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

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