Identification of key amino acids responsible for the distinct aggregation properties of microtubule-associated protein 2 and tau
Open accessAbstract
The carboxyl‐terminal sequence of tau composes the framework for its intracellular inclusions that appear in diverse neurodegenerative disorders known as tauopathies. However, microtubule‐associated protein 2 (MAP 2), which contains a homologous carboxyl‐terminal sequence of tau, is undetectable in the mature tau inclusions. The mechanisms underlying this phenomenon have remained largely unknown. Here, we show that tau and MAP 2 have different aggregation properties: tau aggregates to form filaments but MAP 2 remains to be granules. Exchanging 221YKPV224 of tau (0N3R) near the PHF 6 motif for 340TKKI343 of MAP 2c profoundly changed aggregation properties, suggesting that the YKPV motif is important for filament formation, whereas the TKKI motif is for granule formation. Thus, these minimal sequences may determine the different fates of tau and MAP 2 in the formation of inclusions in tauopathies. image Tau and microtubule‐associated protein 2 (MAP2) are homologous microtubule‐associated proteins in neurons. So far, it is largely unknown why tau but not MAP2 is selectively involved in the filamentous inclusions (neurofibrillary tangles, NFT) formation in tauopathies, including Alzheimer's disease. In this study, we found that the difference of only two amino acids in tau and MAP2 sequences may determine their different fates in tauopathies. These results may lead to the elucidation of tau deregulation in pathological conditions.
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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 [33]
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- Authors
- Xie, C., Soeda, Y., Shinzaki, Y., In, Y., Tomoo, K., Ihara, Y., & Miyasaka, T.
- Affiliations
- Doshisha University (JP)
- Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (JP)
- Osaka University of Pharmaceutical Sciences (JP)
- Corresponding author
- Miyasaka, Tomohiro
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2015-08-26
- Volume
- 135
- Issue
- 1
- Pages
- 19-26
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC5049617
- OpenAlex
- W1878810938
- Cited by
- 27
- References
- 17
- Citations by year
- 2024: 2 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 2
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neurochemistry (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Grant-in-Aid for Scientific Research KAKENHI
- Grant-in-Aid for Young Scientists (B) (20700324, 24700368)
- Grant-in-Aid for Challenging Exploratory Research (22650074)
- Core Research for Evolutional Science and Technology CREST
- Japan Science and Technology Agency (JST)
- Japan Society for the Promotion of Science (JSPS)
- Grant-in-Aid for Scientific Research on Innovative Areas (26117004)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau protein, MAP2, tauopathy, protein aggregation, neurofibrillary tangles, carboxyl-terminal sequence, filamentation, granule formation, Alzheimer's disease, neurodegeneration
- MeSH terms
- Alzheimer Disease, Amino Acids, Humans, Microtubule-Associated Proteins, Neurons, Neurofibrillary Tangles, tau Proteins, Tauopathies
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