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dc.contributor.authorAltawashi, Azza
dc.contributor.authorJung, Sung Yun
dc.contributor.authorLiu, Dou
dc.contributor.authorSu, Bing
dc.contributor.authorQin, Jun
dc.date.accessioned2014-11-11T14:30:09Z
dc.date.available2014-11-11T14:30:09Z
dc.date.issued2012-02-28
dc.identifier.citationAl-Tawashi A, Jung SY, Liu D, Su B, Qin J (2012) Protein Implicated in Nonsyndromic Mental Retardation Regulates Protein Kinase A (PKA) Activity. Journal of Biological Chemistry 287: 14644-14658. doi:10.1074/jbc.M111.261875.
dc.identifier.issn00219258
dc.identifier.pmid22375002
dc.identifier.doi10.1074/jbc.M111.261875
dc.identifier.urihttp://hdl.handle.net/10754/334571
dc.description.abstractMutation of the coiled-coil and C2 domain-containing 1A (CC2D1A) gene, which encodes a C2 domain and DM14 domain-containing protein, has been linked to severe autosomal recessive nonsyndromic mental retardation. Using a mouse model that produces a truncated form of CC2D1A that lacks the C2 domain and three of the four DM14 domains, we show that CC2D1A is important for neuronal differentiation and brain development. CC2D1A mutant neurons are hypersensitive to stress and have a reduced capacitytoformdendritesandsynapsesinculture. Atthebiochemical level,CC2D1Atransduces signals to the cyclic adenosine 3?,5?-monophosphate (cAMP)-protein kinase A (PKA) pathway during neuronal cell differentiation. PKA activity is compromised, and the translocation of its catalytic subunit to the nucleus is also defective in CC2D1A mutant cells. Consistently, phosphorylation of the PKA target cAMP-responsive element-binding protein, at serine 133, is nearly abolished in CC2D1A mutant cells. The defects in cAMP/PKA signaling were observed in fibroblast, macrophage, and neuronal primary cells derived from the CC2D1A KO mice. CC2D1A associates with the cAMP-PKA complex following forskolin treatment and accumulates in vesicles or on the plasma membrane in wild-type cells, suggesting that CC2D1A may recruit the PKA complex to the membrane to facilitate signal transduction. Together, our data show that CC2D1A is an important regulator of the cAMP/PKA signaling pathway, which may be the underlying cause for impaired mental function in nonsyndromic mental retardation patients with CC2D1A mutation. 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
dc.language.isoen
dc.publisherAmerican Society for Biochemistry & Molecular Biology (ASBMB)
dc.rightsAuthor's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
dc.rightsArchived with thanks to Journal of Biological Chemistry
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/
dc.subjectBrain development
dc.subjectCatalytic subunits
dc.subjectCoiled coil
dc.subjectCyclic adenosine
dc.subjectDomain-containing proteins
dc.subjectElement-binding proteins
dc.subjectForskolin
dc.subjectMental retardation
dc.subjectMonophosphates
dc.subjectMouse models
dc.subjectMutant cells
dc.subjectNeuronal cell
dc.subjectNeuronal differentiation
dc.subjectPrimary cells
dc.subjectProtein kinase A
dc.subjectSignaling pathways
dc.subjectUnderlying cause
dc.subjectWild-type cells
dc.subjectAmino acids
dc.subjectCell culture
dc.subjectCell membranes
dc.subjectEnzymes
dc.subjectGenes
dc.subjectHandicapped persons
dc.subjectMammals
dc.subjectPhosphorylation
dc.subjectSignal transduction
dc.subjectProteins
dc.subjectcyclic AMP dependent protein kinase
dc.subjectcyclic AMP responsive element binding protein
dc.subjectforskolin
dc.subjectphosphatidic acid
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectarticle
dc.subjectbrain development
dc.subjectcell mutant
dc.subjectcell nucleus
dc.subjectcellular stress response
dc.subjectcoiled coil and C2 domain containing 1A gene
dc.subjectcontrolled study
dc.subjectdendrite
dc.subjectdevelopmental gene
dc.subjectenzyme active site
dc.subjectenzyme phosphorylation
dc.subjectenzyme substrate complex
dc.subjectfemale
dc.subjectfibroblast
dc.subjectgene function
dc.subjectgene location
dc.subjectmacrophage
dc.subjectmembrane binding
dc.subjectmental deficiency
dc.subjectmouse
dc.subjectnerve cell differentiation
dc.subjectnerve cell plasticity
dc.subjectneuropathology
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectprotein targeting
dc.subjectsignal transduction
dc.subjectsynapse
dc.subjectwild type
dc.subjectActive Transport, Cell Nucleus
dc.subjectAnimals
dc.subjectBrain
dc.subjectCell Line
dc.subjectCell Nucleus
dc.subjectCyclic AMP-Dependent Protein Kinases
dc.subjectDNA-Binding Proteins
dc.subjectGenetic Diseases, Inborn
dc.subjectHumans
dc.subjectIntellectual Disability
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectNerve Tissue Proteins
dc.subjectNeurons
dc.subjectProtein Structure, Tertiary
dc.subjectRepressor Proteins
dc.subjectResponse Elements
dc.subjectSignal Transduction
dc.subjectMus
dc.titleProtein implicated in nonsyndromic mental retardation regulates protein kinase A (PKA) activity
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.identifier.journalJournal of Biological Chemistry
dc.identifier.pmcidPMC3340277
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionCenter for Molecular Discovery, Verna and Marrs McLean Depts. of Biochem. and Molecular Biology and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, United States
dc.contributor.institutionDepartment of Immunobiology and Program of Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06520, United States
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personAltawashi, Azza
refterms.dateFOA2018-06-13T15:52:06Z
dc.date.published-online2012-02-28
dc.date.published-print2012-04-27


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Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
Except where otherwise noted, this item's license is described as Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles