Functional effects of tau gene mutations ΔN296 and N296H
Open accessAbstract
Mutations in the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome‐17 (FTDP‐17). Functionally, about half of the known mutations increase the alternative mRNA splicing of exon 10 of the tau gene, resulting in the overproduction of tau isoforms with four microtubule‐binding repeats. The other mutations reduce the ability of tau to interact with microtubules, with some mutations also increasing the propensity of tau to assemble into filaments. Here we have examined the functional effects of the recently described tau gene mutations ΔN296 and N296H. Both mutations reduced the ability of tau to promote microtubule assembly, without having a significant effect on tau filament formation. By exon trapping, they increased the splicing of exon 10. ΔN296 and N296H thus define a class of tau mutations with effects at both the RNA and the protein level.
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N296H causes increased inclusion of MAPT exon 10, leading to an overrepresentation of tau isoforms with four microtubule-binding repeats (4R tau).
“Like many other familial FTD mutations (Denk and Wade-Martins, 2009), N296H causes increased inclusion of MAPT exon 10, leading to an overrepresentation of tau isoforms with four microtubule-binding repeats, known as 4R tau (Grover et al., 2002; Yoshida et al., 2002).”
From Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice (2017) · cites this paper as Yoshida et al., 2002
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“Similar levels of three-repeat and four-repeat tau isoforms are expressed in normal cerebral cortex (Goedert and Jakes 1990).”
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Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice
Vargas-Caballero, M., Denk, F., Wobst, H. J., Arch, E., Pegasiou, C.-M., Oliver, P. L., Shipton, O. A., Paulsen, O., & Wade-Martins, R. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00201 · Cited by 18 · see citing works
- Authors
- Yoshida, H., Crowther, R. A., & Goedert, M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Goedert, Michel
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2002-01-21
- Volume
- 80
- Issue
- 3
- Pages
- 548-551
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2146592553
- Cited by
- 56
- References
- 1
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 4 · 2013: 2
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Research Trust
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau gene mutations, alternative splicing, tau isoforms, microtubule binding, microtubule assembly, exon trapping
- MeSH terms
- Exons, Humans, Microscopy, Electron, Microtubules, Mutagenesis, Site-Directed, tau Proteins
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