Journal Article

Protein kinase C gamma mutations in spinocerebellar ataxia 14 increase kinase activity and alter membrane targeting

D. S. Verbeek, M. A. Knight, G. G. Harmison, K. H. Fischbeck and B. W. Howell

in Brain

Published on behalf of The Guarantors of Brain

Volume 128, issue 2, pages 436-442
Published in print February 2005 | ISSN: 0006-8950
Published online December 2004 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awh378
Protein kinase C gamma mutations in spinocerebellar ataxia 14 increase kinase activity and alter membrane targeting

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The protein kinase C gamma (PKCγ) gene is mutated in spinocerebellar ataxia type 14 (SCA14). In this study, we investigated the effects of two SCA14 missense mutations, G118D and C150F, on PKCγ function. We found that these mutations increase the intrinsic activity of PKCγ. Direct visualization of labelled PKCγ in living cells demonstrates that the mutant protein translocates more rapidly to selected regions of the plasma membrane in response to Ca2+ influx. These results point to specific alterations in mutant PKCγ function that could lead to the selective neuronal degeneration of SCA14.

Keywords: SCA14; spinocerebellar ataxia; PKCγ; Purkinje cells; DAG = diacylglycerol; FGF = fibroblast growth factor; GFP = green fluorescent protein; LTD = long-term depression; PBS = phosphate-buffered saline; PKC = protein kinase C; SCA14 = spinocerebellar ataxia type 14; TPA = phorbol-12-myristate-13-acetate

Journal Article.  4973 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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