The schizophrenia-associated variant in SLC39A8 alters protein glycosylation in the mouse brain
| العنوان: | The schizophrenia-associated variant in SLC39A8 alters protein glycosylation in the mouse brain |
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| المؤلفون: | Robert G. Mealer, Sarah E. Williams, Maxence Noel, Bo Yang, Alexandria K. D’Souza, Toru Nakata, Daniel B. Graham, Elizabeth A. Creasey, Murat Cetinbas, Ruslan I. Sadreyev, Edward M. Scolnick, Christina M. Woo, Jordan W. Smoller, Ramnik J. Xavier, Richard D. Cummings |
| المصدر: | Mol Psychiatry |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Manganese, Mice, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Glycosylation, Schizophrenia, Animals, Brain, Cation Transport Proteins, Molecular Biology, Article |
| الوصف: | A missense mutation (A391T) in SLC39A8 is strongly associated with schizophrenia in genomic studies, though the molecular connection to the brain is unknown. Human carriers of A391T have reduced serum manganese, altered plasma glycosylation, and brain MRI changes consistent with altered metal transport. Here, using a knock-in mouse model homozygous for A391T, we show that the schizophrenia-associated variant changes protein glycosylation in the brain. Glycosylation of Asn residues in glycoproteins (N-glycosylation) was most significantly impaired, with effects differing between regions. RNAseq analysis showed negligible regional variation, consistent with changes in the activity of glycosylation enzymes rather than gene expression. Finally, nearly one third of detected glycoproteins were differentially N-glycosylated in the cortex, including members of several pathways previously implicated in schizophrenia, such as cell adhesion molecules and neurotransmitter receptors that are expressed across all cell types. These findings provide a mechanistic link between a risk allele and potentially reversible biochemical changes in the brain, furthering our molecular understanding of the pathophysiology of schizophrenia and a novel opportunity for therapeutic development. |
| تدمد: | 1476-5578 1359-4184 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea5c47be13a681718d11d1f218770b66 https://doi.org/10.1038/s41380-022-01490-1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ea5c47be13a681718d11d1f218770b66 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765578 13594184 |
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