Journal article
Phosphatase inhibition in human neuroblastoma cells alters tau antigenicity and renders it incompetent to associate with exogenous microtubules
FEBS letters, v 380(1), pp 63-67
1996
PMID: 8603748
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The abnormal cytoskeletal organization observed in Alzheimer's disease has been suggested to arise from hyperphosphorylation of tau and the resultant elimination of its ability to associate with microtubules. This possibility has been supported by a number of studies under cell-free conditions utilizing various kinases, phosphatases and their corresponding inhibitors each, and by treatment of intact cells with kinase and phosphatase activators and inhibitors. However, in studies utilizing intact cells, it remained difficult to attribute microtubule compromise specifically to tau hyperphosphorylation due to potential influence of inhibitors on tubulin and/or other microtubule-associated proteins, which themselves possess assembly-regulatory phosphorylation sites. To address this difficulty, we subjected SH-SY 5Y human neuroblastoma cells to treatment with the phosphatase inhibitor okadaic acid (OA), which has been previously demonstrated to depolymerize microtubules in these cells. OA induced an increase in tau hyperphosphorylation as evidenced by an increase in Alz-50 immunoreactivity and a corresponding decrease in Tau-1 immunoreactivity. When tau-enriched fractions from OA-treated cells were incubated under microtubule assembly-promoting conditions with twice-cycled, tau-free preparations of bovine brain tubulin not exposed to OA, Alz-50-immunoreactive tau isoforms displayed a marked (49%) reduction in ability to co-assemble with bovine microtubules as compared with Tau-1-and 5E2-immunoreactive isoforms. These data indicate that hyperphosphorylated tau has a reduced capacity to associate with microtubules, and support the hypothesis that tau hyperphosphorylation may underlie microtubule breakdown in Alzheimer's disease.
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Details
- Title
- Phosphatase inhibition in human neuroblastoma cells alters tau antigenicity and renders it incompetent to associate with exogenous microtubules
- Creators
- Thomas B. Shea - University of Massachusetts LowellItzhak Fischer - Department of Anatomy and Neurobiology, Medical College of Philadelphia, Philadelphia, PA 19129, USA
- Publication Details
- FEBS letters, v 380(1), pp 63-67
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:A1996TV80100014
- Scopus ID
- 2-s2.0-0030046767
- Other Identifier
- 991019168799604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics
- Cell Biology