| First Author | Pettem KL | Year | 2013 |
| Journal | J Cell Biol | Volume | 200 |
| Issue | 3 | Pages | 321-36 |
| PubMed ID | 23358245 | Mgi Jnum | J:195216 |
| Mgi Id | MGI:5476874 | Doi | 10.1083/jcb.201206028 |
| Citation | Pettem KL, et al. (2013) Interaction between autism-linked MDGAs and neuroligins suppresses inhibitory synapse development. J Cell Biol 200(3):321-36 |
| abstractText | Rare variants in MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors), including multiple protein-truncating deletions, are linked to autism and schizophrenia, but the function of these genes is poorly understood. Here, we show that MDGA1 and MDGA2 bound to neuroligin-2 inhibitory synapse-organizing protein, also implicated in neurodevelopmental disorders. MDGA1 inhibited the synapse-promoting activity of neuroligin-2, without altering neuroligin-2 surface trafficking, by inhibiting interaction of neuroligin-2 with neurexin. MDGA binding and suppression of synaptogenic activity was selective for neuroligin-2 and not neuroligin-1 excitatory synapse organizer. Overexpression of MDGA1 in cultured rat hippocampal neurons reduced inhibitory synapse density without altering excitatory synapse density. Furthermore, RNAi-mediated knockdown of MDGA1 selectively increased inhibitory but not excitatory synapse density. These results identify MDGA1 as one of few identified negative regulators of synapse development with a unique selectivity for inhibitory synapses. These results also place MDGAs in the neurexin-neuroligin synaptic pathway implicated in neurodevelopmental disorders and support the idea that an imbalance between inhibitory and excitatory synapses may contribute to these disorders. |
