دورية أكاديمية
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Characterization of six CaMKIIα variants found in patients with schizophrenia.

التفاصيل البيبلوغرافية
العنوان: Characterization of six CaMKIIα variants found in patients with schizophrenia.
المؤلفون: Brown CN; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Cook SG; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Allen HF; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Crosby KC; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Singh T; Stanley Center for Psychiatric Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Coultrap SJ; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Bayer KU; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
المصدر: IScience [iScience] 2021 Sep 27; Vol. 24 (10), pp. 103184. Date of Electronic Publication: 2021 Sep 27 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2018]-
مستخلص: The Ca 2+ /Calmodulin-dependent protein kinase II (CaMKII) is a central regulator of synaptic plasticity and has been implicated in various neurological conditions, including schizophrenia. Here, we characterize six different CaMKIIα variants found in patients with schizophrenia. Only R396stop disrupted the 12-meric holoenzyme structure, GluN2B binding, and synaptic localization. Additionally, R396stop impaired T286 autophosphorylation that generates Ca 2+ -independent "autonomous" kinase activity. This impairment in T286 autophosphorylation was shared by the R8H mutation, the only mutation that additionally reduced stimulated kinase activity. None of the mutations affected the levels of CaMKII expression in HEK293 cells. Thus, impaired CaMKII function was detected only for R396stop and R8H. However, two of the other mutations have been later identified also in the general population, and not all mutations found in patients with schizophrenia would be expected to cause disease. Nonetheless, for the R396stop mutation, the severity of the biochemical effects found here would predict a neurological phenotype.
Competing Interests: K.U.B. is co-founder and board member of Neurexis Therapeutics, a company that seeks to develop a CaMKII inhibitor into a therapeutic drug for cerebral ischemia. The other authors declare that they have nothing to disclose.
(© 2021 The Author(s).)
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معلومات مُعتمدة: R01 AG067713 United States AG NIA NIH HHS; R01 NS081248 United States NS NINDS NIH HHS; T32 GM007635 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Biological sciences; Neuroscience; Protein structure aspects
تواريخ الأحداث: Date Created: 20211020 Latest Revision: 20220329
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8506966
DOI: 10.1016/j.isci.2021.103184
PMID: 34667946
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-0042
DOI:10.1016/j.isci.2021.103184