Human tau becomes phosphorylated and forms filamentous deposits when overexpressed in lamprey central neurons in situ

被引:63
作者
Hall, GF
Yao, J
Lee, G
机构
[1] HARVARD UNIV,SCH MED,DEPT NEUROL NEUROSCI,BOSTON,MA 02115
[2] CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA 02115
关键词
CENTRAL NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; PROTEIN-TAU; NEUROFIBRILLARY TANGLES; MICROTUBULE-BINDING; NEUROFILAMENT PHOSPHORYLATION; CLOSE AXOTOMY; MESSENGER-RNA; LOCALIZATION; PATHOLOGY;
D O I
10.1073/pnas.94.9.4733
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4733 / 4738
页数:6
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