Activation of mutant protein kinase Cgamma leads to aberrant sequestration and impairment of its cellular function |
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Authors: | Doran Graeme Davies Kay E Talbot Kevin |
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Institution: | a MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK b Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK |
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Abstract: | Mutations in protein kinase Cγ (PKCγ) cause the neurodegenerative disease spinocerebellar ataxia type 14 (SCA14). In this study, expression of an extensive panel of known SCA14-associated PKCγ mutations as fusion proteins in cell culture led to the consistent formation of cytoplasmic aggregates in response to purinoceptor stimulation. Aggregates co-stained with antibodies to phosphorylated PKCγ and the early endosome marker EEA1 but failed to redistribute to the cell membrane under conditions of oxidative stress. These studies suggest that Purkinje cell damage in SCA14 may result from a reduction of PKCγ activity due its aberrant sequestration in the early endosome compartment. |
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Keywords: | Spinocerebellar ataxia SCA14 Protein kinase Cγ PKCγ Ataxia |
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