Frontotemporal dementia mutant Tau promotes aberrant Fyn nanoclustering in hippocampal dendritic spines Article Swipe
Pranesh Padmanabhan
,
Ramón Martínez‐Mármol
,
Di Xia
,
Jürgen Götz
,
Frédéric A. Meunier
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.7554/elife.45040
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.7554/elife.45040
The Src kinase Fyn plays critical roles in memory formation and Alzheimer’s disease. Its targeting to neuronal dendrites is regulated by Tau via an unknown mechanism. As nanoclustering is essential for efficient signaling, we used single-molecule tracking to characterize the nanoscale distribution of Fyn in mouse hippocampal neurons, and manipulated the expression of Tau to test whether it controls Fyn nanoscale organization. We found that dendritic Fyn exhibits at least three distinct motion states, two of them associated with nanodomains. Fyn mobility decreases in dendrites during neuronal maturation, suggesting a dynamic synaptic reorganization. Removing Tau increases Fyn mobility in dendritic shafts, an effect that is rescued by re-expressing wildtype Tau. By contrast, expression of frontotemporal dementia P301L mutant Tau immobilizes Fyn in dendritic spines, affecting its motion state distribution and nanoclustering. Tau therefore controls the nanoscale organization of Fyn in dendrites, with the pathological Tau P301L mutation potentially contributing to synaptic dysfunction by promoting aberrant Fyn nanoclustering in spines.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.7554/elife.45040
- OA Status
- gold
- Cited By
- 58
- References
- 75
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2956127026
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2956127026Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.7554/elife.45040Digital Object Identifier
- Title
-
Frontotemporal dementia mutant Tau promotes aberrant Fyn nanoclustering in hippocampal dendritic spinesWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2019Year of publication
- Publication date
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2019-06-25Full publication date if available
- Authors
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Pranesh Padmanabhan, Ramón Martínez‐Mármol, Di Xia, Jürgen Götz, Frédéric A. MeunierList of authors in order
- Landing page
-
https://doi.org/10.7554/elife.45040Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.7554/elife.45040Direct OA link when available
- Concepts
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FYN, Dendritic spine, Hippocampal formation, Neuroscience, Synapse, Biology, Cell biology, Alzheimer's disease, Phosphorylation, Medicine, Proto-oncogene tyrosine-protein kinase Src, Pathology, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
58Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 8, 2024: 10, 2023: 8, 2022: 7, 2021: 10Per-year citation counts (last 5 years)
- References (count)
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75Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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