RRC ID 42696
著者 Mochizuki H, Seki T, Adachi N, Saito N, Mishima HK, Sakai N.
タイトル R659S mutation of gammaPKC is susceptible to cell death: implication of this mutation/polymorphism in the pathogenesis of retinitis pigmentosa.
ジャーナル Neurochem Int
Abstract It has been reported that mutations of gammaPKC cause hereditary spinocerebellar atrophy type 14 (SCA14). Our recent study has revealed that the SCA14 mutant gammaPKC is susceptible to aggregation and causes cell death. Among mutations/polymorphisms of gammaPKC, the R659S mutation was firstly segregated from families with hereditary retinitis pigmentosa type 11 (RP11). Although more reliable etiological mutations of RP11 were subsequently discovered in a human homologue of yeast pre-mRNA splicing gene (PRP31), the role of this R659S missense change in the pathogenicity of RP11 is still controversial. In this study, we overexpressed R659S gammaPKC in CHO cells and characterized the properties of this mutant protein. We found that R659S gammaPKC more prominently induced cell death than did wild-type. This mutant gammaPKC had higher basal activity than wild-type, however, no difference was found in the extent of aggregation and insolubility to detergent between R659S mutant and wild-type. These results suggest that the R659S mutation is susceptible to neuronal death and is involved in the pathogenesis of neurodegenerative diseases, including RP11.
巻・号 49(7)
ページ 669-75
公開日 2006-12-1
DOI 10.1016/j.neuint.2006.05.005
PII S0197-0186(06)00196-3
PMID 16828200
MeSH Animals CHO Cells COS Cells Cell Death / genetics Chlorocebus aethiops Cricetinae Detergents / pharmacology Enzyme Activation / genetics Genetic Predisposition to Disease / genetics* Green Fluorescent Proteins Humans Inclusion Bodies / enzymology Inclusion Bodies / genetics Inclusion Bodies / pathology Mutation / genetics* Photoreceptor Cells, Vertebrate / enzymology Photoreceptor Cells, Vertebrate / pathology Pigment Epithelium of Eye / enzymology Pigment Epithelium of Eye / pathology Pigment Epithelium of Eye / physiopathology Polymorphism, Genetic / genetics* Protein Kinase C / chemistry Protein Kinase C / genetics* Protein Kinase C / metabolism Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / metabolism Retinitis Pigmentosa / enzymology* Retinitis Pigmentosa / genetics* Retinitis Pigmentosa / physiopathology Solubility
IF 3.881
引用数 3
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY NEUROSCIENCES
リソース情報
ヒト・動物細胞