Protein expression of prenyltransferase subunits in postmortem schizophrenia dorsolateral prefrontal cortex
| العنوان: | Protein expression of prenyltransferase subunits in postmortem schizophrenia dorsolateral prefrontal cortex |
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| المؤلفون: | Robert E. McCullumsmith, James H. Meador-Woodruff, Anita Pinner, Toni M. Mueller, Khaled Alganem |
| المصدر: | Translational Psychiatry, Vol 10, Iss 1, Pp 1-9 (2020) Translational Psychiatry |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Upstream and downstream (transduction), Prefrontal Cortex, Molecular neuroscience, Article, Long-term memory, lcsh:RC321-571, Cellular and Molecular Neuroscience, 03 medical and health sciences, 0302 clinical medicine, Palmitoylation, Prenylation, medicine, Animals, Humans, Prefrontal cortex, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, 030304 developmental biology, 0303 health sciences, Chemistry, Intracellular Signaling Peptides and Proteins, Dimethylallyltranstransferase, Protein subcellular localization prediction, Cell biology, Rats, Dorsolateral prefrontal cortex, Psychiatry and Mental health, medicine.anatomical_structure, Synaptic plasticity, Schizophrenia, Protein prenylation, Lipid modification, 030217 neurology & neurosurgery, Antipsychotic Agents |
| الوصف: | The pathophysiology of schizophrenia includes altered neurotransmission, dysregulated intracellular signaling pathway activity, and abnormal dendritic morphology that contribute to deficits of synaptic plasticity in the disorder. These processes all require dynamic protein–protein interactions at cell membranes. Lipid modifications target proteins to membranes by increasing substrate hydrophobicity by the addition of a fatty acid or isoprenyl moiety, and recent evidence suggests that dysregulated posttranslational lipid modifications may play a role in multiple neuropsychiatric disorders, including schizophrenia. Consistent with these emerging findings, we have recently reported decreased protein S-palmitoylation in schizophrenia. Protein prenylation is a lipid modification that occurs upstream of S-palmitoylation on many protein substrates, facilitating membrane localization and activity of key intracellular signaling proteins. Accordingly, we hypothesized that, in addition to palmitoylation, protein prenylation may be abnormal in schizophrenia. To test this, we assayed protein expression of the five prenyltransferase subunits (FNTA, FNTB, PGGT1B, RABGGTA, and RABGGTB) in postmortem dorsolateral prefrontal cortex from patients with schizophrenia and paired comparison subjects (n = 13 pairs). We found decreased levels of FNTA (14%), PGGT1B (13%), and RABGGTB (8%) in schizophrenia. To determine whether upstream or downstream factors may be driving these changes, we also assayed protein expression of the isoprenoid synthases FDPS and GGPS1 and prenylation-dependent processing enzymes RCE and ICMT. We found these upstream and downstream enzymes to have normal protein expression. To rule out effects from chronic antipsychotic treatment, we assayed FNTA, PGGT1B, and RABGGTB in the cortex from rats treated long-term with haloperidol decanoate and found no change in the expression of these proteins. Given the role prenylation plays in localization of key signaling proteins found at the synapse, these data offer a potential mechanism underlying abnormal protein–protein interactions and protein localization in schizophrenia. |
| اللغة: | English |
| تدمد: | 2158-3188 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fac4a4fce5cfce92e5d8b644b703e47aTest http://link.springer.com/article/10.1038/s41398-019-0610-7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fac4a4fce5cfce92e5d8b644b703e47a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21583188 |
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