DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling

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DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling

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Title: DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling
Author: Martin, Pierre-Marie; Stanley, Robert E.; Ross, Adam P.; Freitas, Andiara E.; Moyer, Caitlin E.; Brumback, Audrey C.; Iafrati, Jillian; Stapornwongkul, Kristina S.; Dominguez, Sky; Kivimäe, Saul; Mulligan, Kimberly A.; Pirooznia, Mehdi; McCombie, W. Richard; Potash, James B.; Zandi, Peter P.; Purcell, Shaun M.; Sanders, Stephan J.; Zuo, Yi; Sohal, Vikaas S.; Cheyette, Benjamin N.R.

Note: Order does not necessarily reflect citation order of authors.

Citation: Martin, P., R. E. Stanley, A. P. Ross, A. E. Freitas, C. E. Moyer, A. C. Brumback, J. Iafrati, et al. 2016. “DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling.” Molecular psychiatry :10.1038/mp.2016.184. doi:10.1038/mp.2016.184. http://dx.doi.org/10.1038/mp.2016.184.
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Abstract: Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/β-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals’ brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a Glycogen Synthase Kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9,000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single nucleotide variants (SNVs) in these individuals compared to psychiatrically-unaffected controls. Many of these SNVs alter Wnt/β-catenin signaling activity of the neurally-predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/β-catenin pathway.
Published Version: doi:10.1038/mp.2016.184
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395363/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630523
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