Human tau becomes phosphorylated and forms filamentous deposits when overexpressed in lamprey central neurons in situ
Human tau becomes phosphorylated and forms filamentous deposits when overexpressed in lamprey central neurons in situ
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DOI：
10.1073/pnas.94.9.4733
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发表时间：
1997-04-29
影响因子：
11.1
通讯作者：
Lee, G
中科院分区：
文献类型：
--
作者：
Hall, GF;Yao, J;Lee, G
将编码人类tau （htau）蛋白的质粒微量注射到鉴定的七鳃鳗网状脊髓神经元（前球细胞，或abc）原位诱导慢性htau表达，htau蛋白通过需要htau蛋白c端结构域但不需要定向htau mRNA转运的机制被转运到表达abc的轴突和树突。htau在具有大量htau积累的abc中在PHF-1 （Ser-396/404）和TAU-1/AT8 （Ser-199/202）表位发生磷酸化；许多这样的细胞也表现出退行性变化，其中包括细胞外htau沉积的发展。最后，通过免疫电镜观察，融合绿色荧光蛋白的htau蛋白表达诱导含有htau的体树突细丝的积累。这些结果表明，htau在七鳃鳗abc细胞中的慢性表达可能有助于研究脊椎动物中枢神经元中tau过度磷酸化和纤维形成的细胞机制。
Microinjection of plasmids encoding human tau (htau) protein into identified lamprey reticulospinal neurons (anterior bulbar cells, or ABCs) in situ induces chronic htau expression, htau protein is transported to both the axon and dendrites of expressing ABCs by mechanisms that require the C-terminal domain of htau protein but do not require directed htau mRNA transport, htau becomes phosphorylated at the PHF-1 (Ser-396/404) and TAU-1/AT8 (Ser-199/202) epitopes throughout ABCs with heavy htau accumulations; many such cells also exhibit degenerative changes, which include the development of extracellular htau deposits. Finally, expression of htau protein fused to green fluorescent protein induced the somatodendritic accumulation of filaments containing htau when examined by immunoelectron microscopy. These results suggest that chronic expression of htau in lamprey ABCs may be useful for studying cellular mechanisms underlying tau hyperphosphorylation sand filament formation in vertebrate central neurons in situ.