Increased association between rough endoplasmic reticulum membranes and mitochondria in transgenic mice that express P301L tau
Abstract
In several neurodegenerative diseases, including Alzheimer disease, the neuronal microtubule-associated protein tau becomes hyperphosphorylated, accumulates in the somatodendritic compartment, and aggregates into insoluble filaments. The consequences of the accumulation of hyperphosphorylated tau in the somatodendritic compartment remain poorly characterized at the early stage of disease before the formation of tau insoluble filaments. We investigated the ultrastructural changes induced by this accumulation in the neuronal soma of motor neurons in asymptomatic JNPL3 mice that overexpress mutant tau, P301L. More numerous contacts between rough endoplasmic reticulum (RER) membranes and mitochondria were observed in JNLP3 mice compared with wild-type mice. This correlated with a preferential increase of the amount of tau at the surface of RER membranes but not at the surface of mitochondria, as revealed by tau immunogold labeling. Using a subcellular fractionation procedure, an increased amount of phosphorylated tau was identified in the rough microsome subfraction, wherein the RER marker, ribophorin, was enriched. A similar increase was noted in the rough microsome subfraction isolated from Alzheimer disease brains. The association of hyperphosphorylated tau with ER membranes was confirmed by double immunogold labeling of the subfraction enriched in ER membranes isolated from Alzheimer disease brains. These results suggest that more contacts between RER membranes and mitochondr…
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Mitochondria dysfunction has been demonstrated in tau P301L transgenic mice.
“Mitochondria dysfunction has been demonstrated in tau P301L transgenic mice (92 -94)”
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668 · see citing works
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · see citing works
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A
Züchner, S., Mersiyanova, I. V., Muglia, M., Bissar-Tadmouri, N., Rochelle, J., Dadali, E. L., Zappia, M., Nelis, E., Patitucci, A., Senderek, J., et al. (2004) · Nature Genetics · doi:10.1038/ng1341 · Cited by 1,572 · see citing works
Neocortical Neurofibrillary Tangles Correlate With Dementia Severity in Alzheimer's Disease
Bierer, L. M., Hof, P. R., Purohit, D. P., Carlin, L., Schmeidler, J., Davis, K. L., & Perl, D. P. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540250089017 · Cited by 514 · see citing works
Arendt, T., Stieler, J., Strijkstra, A. M., Hut, R. A., Rüdiger, J., Van der Zee, E. A., Harkany, T., Holzer, M., & Härtig, W. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-18-06972.2003 · Cited by 357 · see citing works
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Roles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003 · see citing works
Mitochondria and Calcium in Alzheimer’s Disease: From Cell Signaling to Neuronal Cell Death
Calvo-Rodriguez, M., & Bacskai, B. J. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.004 · Cited by 254 · see citing works
A role for tau at the synapse in Alzheimer’s disease pathogenesis
Pooler, A. M., Noble, W., & Hanger, D. P. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.09.018 · Cited by 203 · see citing works
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Cartes-Saavedra, B., Ghosh, A., & Hajnóczky, G. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00820-1 · Cited by 126 · see citing works
Ljungberg, M. C., Ali, Y. O., Zhu, J., Wu, C.-S., Oka, K., Zhai, R. G., & Lu, H.-C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr492 · Cited by 107 · see citing works
Role of the Lipid Membrane and Membrane Proteins in Tau Pathology
Bok, E., Leem, E., Lee, B.-R., Lee, J. M., Yoo, C. J., Lee, E. M., & Kim, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.653815 · Cited by 61 · see citing works
Hara, M., Hirokawa, K., Kamei, S., & Uchihara, T. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1097-6 · Cited by 55 · see citing works
- Authors
- Perreault, S., Bousquet, O., Lauzon, M., Paiement, J., & Leclerc, N.
- Affiliations
- Université de Montréal (CA)
- Corresponding author
- Leclerc, Nicole
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-05
- Volume
- 68
- Issue
- 5
- Pages
- 503-514
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W1981287298
- Cited by
- 67
- References
- 7
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 10 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 7 · 2012: 4
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Charcot-Marie-Tooth Association
- York University
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- P301L tau, hyperphosphorylated tau, rough endoplasmic reticulum, mitochondria, ER-mitochondria contact sites, Alzheimer's disease, motor neurons, rough microsomes
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Animals, Antibodies, Monoclonal, Brain, Female, Humans, Leucine, Male, Mice, Transgenic, Microtubule-Associated Proteins, Mitochondria, Mutation, Proline, Spinal Cord, Subcellular Fractions, Microscopy, Immunoelectron, tau Proteins, Receptors, Peptide, Endoplasmic Reticulum, Rough, Microscopy, Electron, Transmission, Qa-SNARE Proteins, Mice
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