Journal article
Two motifs within the tau microtubule-binding domain mediate its association with the hsc70 molecular chaperone
Journal of neuroscience research, Vol.86(12), pp.2763-2773
09/2008
DOI: 10.1002/jnr.21721
PMCID: PMC4271846
PMID: 18500754
Abstract
Tau, a microtubule-associated protein with multiple phosphorylation sites, forms aggregates that correlate with neurodegeneration in Alzheimer Disease and several other neurodegenerative diseases, termed tauopathies. Hsc70 is a highly-expressed constitutive chaperone that can drive conformational change in proteins, prevent the aggregation of its substrates, recognize misfolded substrates, and facilitate their degradation. Here, we show that hsc70 binds to the microtubule-binding domain of tau in vitro and in vivo, without an absolute requirement for tau phosphorylation. Binding requires a carboxy-terminal region of hsc70 comprising its peptide-binding and variable domains. We have identified two hsc70-binding sites on tau and hydrophobic amino acids crucial for hsc70-binding. Interestingly, these hsc70-binding sites correspond to the β-structure elements that have been previously reported to facilitate tau aggregation. Thus, it is possible that hsc70 binding might directly inhibit tau-tau interactions that precede tau oligomerization and aggregation. Our results provide an important stimulus for research into how the hsc70-tau interaction might affect tau fate in normal cells and in disease.
Details
- Title: Subtitle
- Two motifs within the tau microtubule-binding domain mediate its association with the hsc70 molecular chaperone
- Creators
- Mitul Sarkar - Program in Neuroscience, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242Jeff Kuret - Department of Molecular & Cellular Biochemistry, The Ohio State University, Columbus, OH 43210Gloria Lee - Program in Neuroscience, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Journal of neuroscience research, Vol.86(12), pp.2763-2773
- DOI
- 10.1002/jnr.21721
- PMID
- 18500754
- PMCID
- PMC4271846
- NLM abbreviation
- J Neurosci Res
- ISSN
- 0360-4012
- eISSN
- 1097-4547
- Language
- English
- Date published
- 09/2008
- Academic Unit
- Iowa Neuroscience Institute; Immunology; Internal Medicine
- Record Identifier
- 9984065391502771
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