Seshadri, S., Faust, T., Ishizuka, K., Delevich, K., Chung, Y., Kim, S. H., Cowles, M., Niwa, M., Jaaro-Peled, H., Tomoda, T., Lai, C., Anton, E. S., Li, B., Sawa, A. (December 2015) Interneuronal DISC1 regulates NRG1-ErbB4 signalling and excitatory-inhibitory synapse formation in the mature cortex. Nat Commun, 6. p. 10118. ISSN 2041-1723
Abstract
Neuregulin-1 (NRG1) and its receptor ErbB4 influence several processes of neurodevelopment, but the mechanisms regulating this signalling in the mature brain are not well known. DISC1 is a multifunctional scaffold protein that mediates many cellular processes. Here we present a functional relationship between DISC1 and NRG1-ErbB4 signalling in mature cortical interneurons. By cell type-specific gene modulation in vitro and in vivo including in a mutant DISC1 mouse model, we demonstrate that DISC1 inhibits NRG1-induced ErbB4 activation and signalling. This effect is likely mediated by competitive inhibition of binding of ErbB4 to PSD95. Finally, we show that interneuronal DISC1 affects NRG1-ErbB4-mediated phenotypes in the fast spiking interneuron-pyramidal neuron circuit. Post-mortem brain analyses and some genetic studies have reported interneuronal deficits and involvement of the DISC1, NRG1 and ErbB4 genes in schizophrenia, respectively. Our results suggest a mechanism by which cross-talk between DISC1 and NRG1-ErbB4 signalling may contribute to these deficits.
| Item Type: | Paper |
|---|---|
| CSHL Authors: | |
| Communities: | CSHL labs > Li lab School of Biological Sciences > Publications |
| Depositing User: | Matthew Dunn |
| Date: | 11 December 2015 |
| Date Deposited: | 14 Dec 2020 18:04 |
| Last Modified: | 01 Mar 2024 14:49 |
| PMCID: | PMC4682104 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/39639 |
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