ArticleFrontiers in molecular neuroscience2014
Premature lethality, hyperactivity, and aberrant phosphorylation in transgenic mice expressing a constitutively active form of Fyn.
Article in Frontiers in molecular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- WAVE complex forms linear arrays at negative membrane curvature to instruct lamellipodia formation.The Journal of cell biology · 2025Article
- Fyn-dependent Tau microcluster formation seeds and boosts extensive Tau pathology.Acta neuropathologica · 2025Article
- Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Disentangling tau: One protein, many therapeutic approaches.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Location, location, location: Protein kinase nanoclustering for optimised signalling output.eLife · 2024Review
- Enhanced Fyn-tau and NR2B-PSD95 interactions in epileptic foci in experimental models and human epilepsy.Brain communications · 2024Article
- Aberrant palmitoylation caused by a ZDHHC21 mutation contributes to pathophysiology of Alzheimer's disease.BMC medicine · 2023Article
- Fyn nanoclustering requires switching to an open conformation and is enhanced by FTLD-Tau biomolecular condensates.Molecular psychiatry · 2023Article
- Fyn-tau Ablation Modifies PTZ-Induced Seizures and Post-seizure Hallmarks of Early Epileptogenesis.Frontiers in cellular neuroscience · 2020Article
- Frontotemporal dementia mutant Tau promotes aberrant Fyn nanoclustering in hippocampal dendritic spines.eLife · 2019Article
- Targeting Fyn Kinase in Alzheimer's Disease.Biological psychiatry · 2018Review
- Pyk2 is a Novel Tau Tyrosine Kinase that is Regulated by the Tyrosine Kinase Fyn.Journal of Alzheimer's disease : JAD · 2018Article
- Somatodendritic accumulation of Tau in Alzheimer's disease is promoted by Fyn-mediated local protein translation.The EMBO journal · 2017Article
- Co-immunoprecipitation with Tau Isoform-specific Antibodies Reveals Distinct Protein Interactions and Highlights a Putative Role for 2N Tau in Disease.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The kinase Fyn, the microtubule-associated protein tau and the peptide amyloid-β (Aβ) constitute a toxic triad in Alzheimer's disease (AD). Tau's subcellular localization is mainly regulated by phosphorylation whereas Fyn's localization is dictated by palmitoylation targeting it to the plasma membrane in a reversible manner. We have previously shown that tau is required for Fyn to be targeted to the dendritic spine. We had also shown that a truncated form of tau (Δtau) that accumulates in the cell soma is capable of trapping Fyn and preventing it from entering the spine. Here we determined that palmitoylation is required for Fyn's membrane and spine localization. We further evaluated the functional consequences of neuronal over-expression of the constitutively active Y531F mutant form of Fyn (FynCA) in transgenic mice. We found that the FynCA transgenic mice displayed a reduced weight, a massively reduced lifespan and a high level of hyperactivity. The lifespan of the FynCA mice was only slightly extended by crossing them with Δtau transgenic mice, possibly reflecting differences in expression patterns of the transgenes and high levels of transgenic FynCA compared to endogenous Fyn. Analysis of synaptosomes revealed that FynCA accumulated at high levels in the spine, resulting in increased levels of the NMDA receptor subunit NR2b phosphorylated at residue Y1472. Tau was strongly phosphorylated at the AT8 epitope S202/T205 as shown by Western blot and immunohistochemistry indicating that an increased tyrosine kinase activity of Fyn has down-stream consequences for serine/threonine-directed phosphorylation.
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