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| Neuroligins mediate excitatory and inhibitory synapse formation - Involvement of PSD-95 and neurexin-1 beta in neuroligin-induced synaptic specificity |
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| Author(s): Levinson JN, Chery N, Huang K, Wong TP, Gerrow K, Kang R, Prange O, Wang YT, El-Husseini A |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 280 Issue: 17 Pages: 17312-17319 Published: APR 29 2005 |
| Times Cited: 72 References: 38 |
| Abstract: The balance between excitatory and inhibitory synapses is a tightly regulated process that requires differential recruitment of proteins that dictate the specificity of newly formed contacts. However, factors that control this process remain unidentified. Here we show that members of the neuroligin (NLG) family, including NLG1, NLG2, and NLG3, drive the formation of both excitatory and inhibitory presynaptic contacts. The enrichment of endogenous NLG1 at excitatory contacts and NLG2 at inhibitory synapses supports an important in vivo role for these proteins in the development of both types of contacts. Immunocytochemical and electrophysiological analysis showed that the effects on excitatory and inhibitory synapses can be blocked by treatment with a fusion protein containing the extracellular domain of neurexin-1 beta. We also found that overexpression of PSD-95, a postsynaptic binding partner of NLGs, resulted in a shift in the distribution of NLG2 from inhibitory to excitatory synapses. These findings reveal a critical role for NLGs and their synaptic partners in controlling the number of inhibitory and excitatory synapses. Furthermore, relative levels of PSD-95 alter the ratio of excitatory to inhibitory synaptic contacts by sequestering members of the NLG family to excitatory synapses. |
| Document Type: Article |
| Language: English |
| Reprint Address: El-Husseini, A (reprint author), Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC V6T 1Z3 Canada |
Addresses:
1. Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC V6T 1Z3 Canada
2. Univ British Columbia, Dept Med, Brain Res Ctr, Vancouver, BC V6T 1Z3 Canada |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 919JY |
| ISSN: 0021-9258 |
| DOI: 10.1074/jbc.M413812200 |
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