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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Qiang, Yuan Lee, Dongmin Kim, Hyun Südhof, Thomas C. Lee, Sung-jin Ko, Jaewon Lee, Kangduk Kim, Yoonji Je, H. Shawn Lee, Hyun Woo |
| Description | Author Affiliation: Lee K ( Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.); |
| Abstract | The MAM domain-containing GPI anchor proteins MDGA1 and MDGA2 are Ig superfamily adhesion molecules composed of six IG domains, a fibronectin III domain, a MAM domain, and a GPI anchor. MDGAs contribute to the radial migration and positioning of a subset of cortical neurons during early neural development. However, MDGAs continue to be expressed in postnatal brain, and their functions during postnatal neural development remain unknown. Here, we demonstrate that MDGAs specifically and with a nanomolar affinity bind to neuroligin-2, a cell-adhesion molecule of inhibitory synapses, but do not bind detectably to neuroligin-1 or neuroligin-3. We observed no cell adhesion between cells expressing neuroligin-2 and MDGA1, suggesting a cis interaction. Importantly, RNAi-mediated knockdown of MDGAs increased the abundance of inhibitory but not excitatory synapses in a neuroligin-2-dependent manner. Conversely, overexpression of MDGA1 decreased the numbers of functional inhibitory synapses. Likewise, coexpression of both MDGA1 and neuroligin-2 reduced the synaptogenic capacity of neuroligin-2 in an artificial synapse-formation assay by abolishing the ability of neuroligin-2 to form an adhesion complex with neurexins. Taken together, our data suggest that MDGAs inhibit the activity of neuroligin-2 in controlling the function of inhibitory synapses and that MDGAs do so by binding to neuroligin-2. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 1 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Adhesion Molecules, Neuronal Metabolism Immunoglobulins Membrane Glycoproteins Nerve Tissue Proteins Neurons Cytology Synapses Physiology Animals Cell Adhesion DNA Primers Genetics GPI-Linked Proteins Genetic Vectors HEK293 Cells Hippocampus Immunoblotting Immunohistochemistry In Situ Hybridization Microscopy, Fluorescence Neural Cell Adhesion Molecules RNA Interference Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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