Doran Graeme, Davies Kay E, Talbot Kevin
MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Biochem Biophys Res Commun. 2008 Aug 1;372(3):447-53. doi: 10.1016/j.bbrc.2008.05.072. Epub 2008 May 27.
Mutations in protein kinase Cgamma (PKCgamma) cause the neurodegenerative disease spinocerebellar ataxia type 14 (SCA14). In this study, expression of an extensive panel of known SCA14-associated PKCgamma 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 PKCgamma 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 PKCgamma activity due its aberrant sequestration in the early endosome compartment.
蛋白激酶Cγ（PKCγ）突变会导致神经退行性疾病14型脊髓小脑共济失调（SCA14）。在本研究中，在细胞培养物中将大量已知的与SCA14相关的PKCγ突变作为融合蛋白表达，在嘌呤受体刺激下会一致形成细胞质聚集体。聚集体与磷酸化PKCγ抗体和早期内体标志物EEA1共同染色，但在氧化应激条件下未能重新分布到细胞膜。这些研究表明，SCA14中浦肯野细胞损伤可能是由于PKCγ在早期内体区室中异常隔离导致其活性降低所致。
