| Microtubule-associated protein tau is hyperphosphorylated during mitosis in the human neuroblastoma cell line SH-SY5Y. | |
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MedLine Citation:
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PMID: 7925819 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A phosphorylated tau epitope specific for paired helical filaments in Alzheimer's disease is recognized by monoclonal antibody PHF-1. Healthy adult brains lack the PHF-1 epitope (PHF-1 tau), but it is transiently expressed by immature neurons during development. We have found that proliferating SH-SY5Y human neuroblastoma cells also express PHF-1 tau. Consistent with the recent finding that cell-cycle-dependent kinases can phosphorylate tau in vitro, flow cytometry showed that mitotic SH-SY5Y cells were up to 18-fold more PHF-1 immunoreactive than nonmitotic cells. On immunoblots, PHF-1 tau in mitotic and nonmitotic cells also was strikingly different. First, mitosis induced a prominent PHF-1 reactive band at 120 kDa, which likely accounted for the large increase in PHF-1 signal seen at mitosis. Although the size of the 120-kDa band is consistent with it being the high-molecular-weight form of tau, other antibodies to tau did not recognize it. Second, mitosis caused a hyperphosphorylation of the PHF-1 immunoreactive tau band normally seen at 50 kDa. In mitotic cells this band had an increased intensity and molecular weight. Alkaline phosphatase treatment abolished tau M(r) heterogeneity, verifying that the variations in mobility were due to phosphorylation. These data show that cell-cycle-dependent hyperphosphorylation of tau occurs in intact cells, and they support the hypothesis that aberrant activity of cell-cycle-dependent kinases may contribute to tau phosphorylation and PHF formation in Alzheimer's disease. |
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Authors:
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W B Pope; M P Lambert; B Leypold; R Seupaul; L Sletten; G Krafft; W L Klein |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Experimental neurology Volume: 126 ISSN: 0014-4886 ISO Abbreviation: Exp. Neurol. Publication Date: 1994 Apr |
Date Detail:
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Created Date: 1994-11-17 Completed Date: 1994-11-17 Revised Date: 2011-08-02 |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 185-94 Citation Subset: IM |
Affiliation:
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Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Alzheimer Disease / metabolism, pathology Amino Acid Sequence Antibodies, Monoclonal Biological Markers / analysis Cell Line Consensus Sequence Fluorescent Antibody Technique Humans Immunoblotting Mitosis* Molecular Sequence Data Neuroblastoma / metabolism*, pathology Reference Values Tumor Cells, Cultured tau Proteins / analysis, chemistry, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AG09337/AG/NIA NIH HHS; AG10481/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Biological Markers; 0/PHF-1 monoclonal antibody; 0/tau Proteins |
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