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Cited by 28Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

The Homologous Carboxyl-Terminal Domains of Microtubule-Associated Protein 2 and TAU Induce Neuronal Dysfunction and Have Differential Fates in the Evolution of Neurofibrillary Tangles

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Xie, Ce, Miyasaka, Tomohiro, Yoshimura, Satomi, Hatsuta, Hiroyuki, Yoshina, Sawako, Kage-Nakadai, Eriko, Mitani, Shohei, Murayama, Shigeo +1 more·2014·PLoS ONE
DOI 10.1371/journal.pone.0089796PMC PMC3934940
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Abstract

Microtubule-associated protein 2 (MAP2) and Tau are abundant neuronal microtubule-associated proteins. Both proteins have highly homologous carboxyl-terminal sequences that function as microtubule-binding domains. Whereas Tau is widely accepted as a pathoetiological factor in human tauopathies, including Alzheimer's disease (AD), it is not known whether there is a relationship between MAP2 and tauopathy. To better understand the pathological roles of MAP2 and Tau, we compared their behaviors in transgenic Caenorhabditis elegans in which MAP2 or Tau was expressed pan-neuronally. Both MAP2 and Tau elicited severe neuronal dysfunction and neuritic abnormalities, despite the absence of detergent-insoluble aggregates in worm neurons. Biochemical analysis revealed that the expressed MAP2 or Tau in worms was highly phosphorylated and did not bind to microtubules. Newly raised antibodies to MAP2 that effectively distinguished between the highly homologous carboxyl-terminal sequences of MAP2 and Tau showed that MAP2 was not involved in the growth process of neurofibrillary tangles in the AD brain. These results indicate that Tau and MAP2 have different fates in the inclusion formation and raise the possibility that MAP2 plays a significant role in neurotoxicity in the AD brain despite the absence of MAP2-aggregates.

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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 [32]

    The Results section (‘Tau but not MAP2c forms ThT-positive, insoluble aggregates in the presence of heparin’; page unavailable) reports an in vitro aggregation assay in which MAP2c showed a small, early increase in ThT fluorescence but formed fewer stable aggregates than Tau. It does not identify MAP2c aggregates as granular or establish that they are non-amyloidogenic—the portion of the sentence attributed to this source. (LLM, conf=0.83)

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Cited by

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Authors
Xie, C., Miyasaka, T., Yoshimura, S., Hatsuta, H., Yoshina, S., Kage-Nakadai, E., Mitani, S., Murayama, S., & Ihara, Y.
Affiliations
  • Doshisha University (JP)
  • Tokyo Metropolitan Institute of Gerontology (JP)
  • Tokyo Women's Medical University (JP)
Corresponding author
Miyasaka, Tomohiro
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-02-25
Volume
9
Issue
2
Pages
e89796
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0089796
PMC
PMC3934940
OpenAlex
W2088133560
Cited by
28
References
6
Citations by year
2025: 1 · 2024: 1 · 2023: 6 · 2022: 6 · 2021: 2 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3
FWCI
1.33
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Japan Society for the Promotion of Science (20700324, 221S0003, 23790256, 24390053, 22650074, 24700368, CREST)
  • Japan Science and Technology Agency (CREST)
  • Core Research for Evolutional Science and Technology
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
MAP2, tau protein, C-terminal domain, neurofibrillary tangles, Alzheimer's disease, tauopathy, neuronal dysfunction, microtubule binding, protein phosphorylation, transgenic Caenorhabditis elegans, neurotoxicity, inclusion formation
MeSH terms
Analysis of Variance, Animals, Fluorescent Antibody Technique, Humans, Microtubule-Associated Proteins, Phosphorylation, Blotting, Western, Neurofibrillary Tangles, tau Proteins, Caenorhabditis elegans, Protein Structure, Tertiary, Tauopathies

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