Use of a phosphosensor dye in proteomic analysis of human mutant tau transgenic mice
Use of a phosphosensor dye in proteomic analysis of human mutant tau transgenic mice
复制标题
磷酸传感器染料在人类突变 tau 转基因小鼠蛋白质组学分析中的应用
作者：
M. Takano;M. Otani;Akiko Sakai;K. Kadoyama;S. Matsuyama;Akira Matsumoto;M. Takenokuchi;M. Sumida;T. Taniguchi
最近，我们培育了携带人类N279K突变tau的转基因小鼠（指定为SJLB），这是与17号染色体相关的导致帕金森病的tau突变之一（FTDP-17）。SJLB小鼠模仿阿尔茨海默病患者的一些行为改变和神经病理特征。为了研究tau功能障碍如何导致这些特征，我们在二维聚丙烯酰胺凝胶电泳分析和质谱分析中使用磷酸传感器染料检测了SJLB小鼠海马蛋白的表达和磷酸化水平。钙调钙蛋白和微管蛋白与热休克同源的71 kDa蛋白、微管蛋白和bgr；2、液泡ATP合成酶催化亚基A， &agr；agr -internexin;-烯醇化酶、泛素羧基末端水解酶同工酶L1和复合体素-2在SJLB小鼠中的磷酸化水平明显低于对照小鼠。这些蛋白可能成为阐明神经退行性疾病的潜在机制和治疗干预的新靶点。
Recently, we have generated transgenic mice (designated as SJLB) carrying human N279K mutant tau, one of the tau mutations causing parkinsonism linked to chromosome 17 (FTDP-17). SJLB mice mimic some features of behavioral alterations and neuronal pathology of patients with Alzheimer's disease. To investigate how tau dysfunctions cause these features, we examined the expression and phosphorylation levels in SJLB mouse hippocampal proteins using a phosphosensor dye in two-dimensional poly acrylamide gel electrophoresis analysis and mass spectrometry. Calreticulin and tubulin &bgr;4 are significantly more phosphorylated, and heat shock cognate 71 kDa protein, tubulin &bgr;2, vacuolar ATP synthase catalytic subunit A, &agr;-internexin, &agr;-enolase, ubiquitin carboxyl-terminal hydrolase isozyme L1, and complexin-2 are significantly less phosphorylated in SJLB mice than control mice. These proteins could be new targets for elucidating underlying mechanisms and therapeutic intervention in neurodegenerative diseases.
脑微管相关蛋白在体外调节微管动态不稳定性。
影响因子：
4
作者：
Pryer,NK;Walker,RA;Skeen,VP;Bourns,BD;Soboeiro,MF;Salmon,ED
通讯作者：
Salmon,ED