In vitro polymerization of embryonic MAP-2c and fragments of the MAP-2 microtubule binding region into structures resembling paired helical filaments
Open accessAbstract
The microtubule-associated protein Tau is widely regarded as the principal component of paired helical filaments comprising Alzheimer neurofibrillary tangles. Tau fragments containing the non-identical repeat region formed structures resembling paired helical filaments (Schweers, O., Mandelkow, M., Biernat, J., and Mandelkow, E. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 8463-8467). MAP-2, the other structurally related neuronal microtubule-associated protein, has not been implicated in paired helical filament formation. We now describe the assembly of paired helical filament-like structures from MAP-2 polypeptides containing only 100 residues. A dimeric species, stabilized by an interchain disulfide, appears to be involved in the assembly reaction. We also investigated the polymerization of embryonic MAP-2c, which, except for its microtubule binding region, is structurally distinct from Tau. Full-length MAP-2c formed paired helical filament-like polymers. Polymerized MAP-2c and the microtubule binding region fragment readily bound thioflavin-S, a dye that stains paired helical filaments in the histochemical diagnosis of Alzheimer's disease. Our unprecedented finding that a small MAP-2 microtubule binding region fragment and MAP-2c can form structures resembling straight filaments or Pronase-treated paired helical filaments raises fundamental questions concerning the role of MAP-2 in the pathobiology of Alzheimer disease.
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In vitro experiments have demonstrated that MAP2 forms either fibrillar or granular, non-amyloidogenic aggregates.
“In vitro experiments have demonstrated that MAP2 forms either fibrillar (30, 31) or granular, non-amyloidogenic aggregates (32, 33).”
From MAP2 caps tau fibrils and inhibits aggregation (2023) · cites this paper as [30]
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Cites
THE FINE STRUCTURE OF NEUROFIBRILLARY TANGLES IN ALZHEIMERʼS DISEASE
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Actin and microtubules in neurite initiation: Are MAPs the missing link?
Dehmelt, L., & Halpain, S. (2003) · Journal of Neurobiology · doi:10.1002/neu.10284 · Cited by 236 · see citing works
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Mitotic phosphoepitopes precede paired helical filaments in Alzheimer’s disease
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MAP2c, but Not Tau, Binds and Bundles F-Actin via Its Microtubule Binding Domain
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“However, even though Even though MAP2 and tau share similar microtubulestabilizing activities, their cellular functions are presum- MAP2 can aggregate into filaments under similar in vitro conditions [30], there has been little evidence to date ably not redundant.”
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“There are a number of existing studies that have investigated the change in MAP2 in AD, but the majority of these have examined the possible relationship between MAP2 and the formation of neurofibrillary tangles [11, 12 , 28, 37, 38, 42, 45, 51].”
ResultNoto, L. D., Deture, M., & Purich, D. (2005) · Microscopy research and technique (Print) · doi:10.1002/jemt.20195 · Cited by 28 · see citing works
“Given the fact that the Tau-S-S-Tau dimer was widely regarded as a compulsory intermediate in filament formation (Schweers et al., 1995; DeTure et al., 1996), we were surprised to find that the Tau-S-S-G conjugate underwent rapid filament assembly in the presence of tRNA and other polyanions.”
BackgroundInfluentialSelf-citationIn Vitro Assembly of Alzheimer-like Filaments
DeTure, M. A., Di Noto, L., & Purich, D. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201201200 · Cited by 21 · see citing works
Self-citationDisulfide-cross-linked tau and MAP2 homodimers readily promote microtubule assembly.
Noto, L. D., Deture, M., & Purich, D. (1999) · Molecular Cell Biology Research Communications · doi:10.1006/mcbr.1999.0153 · Cited by 17 · see citing works
Self-citationMAP2 caps tau fibrils and inhibits aggregation
Holden, M. R., Krzesinski, B. J., Weismiller, H. A., Shady, J. R., & Margittai, M. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104891 · Cited by 13 · see citing works
Do aluminium and/or glutamate induce Alzheimer PHF-like formation? An electron microscopic study
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Bolmont, T. (2006) · edoc (University of Basel) · doi:10.5451/unibas-004159594
- Authors
- DeTure, M. A., Yi Zhang, E., Bubb, M. R., & Purich, D. L.
- Affiliations
- University of Florida Health (US)
- Corresponding author
- Purich, Daniel L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-12
- Volume
- 271
- Issue
- 51
- Pages
- 32702-32706
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2168743023
- Cited by
- 18
- References
- 27
- Citations by year
- 2024: 1 · 2023: 1 · 2018: 1
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Florida
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- MAP2, paired helical filaments, microtubule-associated proteins, microtubule-binding region, protein polymerization, Alzheimer's disease, neurofibrillary tangles, tau protein, disulfide-linked dimer, embryonic brain
- MeSH terms
- Amino Acid Sequence, Animals, Cattle, Microscopy, Electron, Microtubule-Associated Proteins, Molecular Sequence Data, Peptide Fragments, Protein Binding, Recombinant Proteins, Repetitive Sequences, Nucleic Acid, Spectrometry, Fluorescence, Neurofibrillary Tangles, Rats
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