Hall G F, Yao J, Lee G
Department of Biological Sciences, University of Massachusetts, Lowell, MA 01854, USA.
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4733-8. doi: 10.1073/pnas.94.9.4733.
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 and filament formation in vertebrate central neurons in situ.
将编码人tau（htau）蛋白的质粒显微注射到已鉴定的七鳃鳗网状脊髓神经元（前延髓细胞，或ABCs）中，可原位诱导htau蛋白的长期表达。htau蛋白通过需要htau蛋白C末端结构域但不需要定向htau mRNA转运的机制，被转运到表达ABCs的轴突和树突中。在整个ABCs中，htau在PHF-1（Ser-396/404）和TAU-1/AT8（Ser-199/202）表位处发生磷酸化，且htau大量积累；许多这样的细胞还表现出退行性变化，包括细胞外htau沉积物的形成。最后，当通过免疫电子显微镜检查时，与绿色荧光蛋白融合的htau蛋白的表达诱导了含有htau的细丝在胞体树突中的积累。这些结果表明，htau在七鳃鳗ABCs中的长期表达可能有助于研究脊椎动物中枢神经元原位tau过度磷酸化和细丝形成的细胞机制。
