Abnormally phosphorylated tau in SY5Y human neuroblastoma cells.
In Alzheimer disease (AD) the microtubule associated protein (MAP) tau is hyperphosphorylated at several sites. In the present study, like AD tau, tau in the human neuroblastoma SH-SY5Y was found to be hyperphosphorylated, at Ser-199/202, Thr-231, Ser-396 and Ser-404. However, in contrast to AD, the tau in SY5Y cells was not hyperphosphorylated at Ser-235 and there was only one tau isoform. Quantitative analysis revealed that approximately 80% of the SY5Y-tau was phosphorylated at Ser-199/202. The phosphorylated tau was deposited in perikarya and processes of the cells whereas most of the unphosphorylated (at Ser-199/202) tau was localized in the nucleus. Tau from the cell lysates did not bind to taxol-stabilized microtubules. In contrast, MAP1b and MAP2 from cell lysates bound to stabilized microtubules in vitro and were associated to the microtubule network in situ. Phosphorylation of tau at high levels, its inactivity with microtubules and its accumulation in SY5Y cells provide for the first time a cell model of cytoskeletal changes seen in AD.
Tanaka
T
T
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Iqbal
K
K
Trenkner
E
E
Liu
D J
DJ
Grundke-Iqbal
I
I
D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D012694:Serine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D012694:Serine