Bin1 directly remodels actin dynamics through its BAR domain
Open accessAbstract
Endocytic processes are facilitated by both curvature-generating BAR-domain proteins and the coordinated polymerization of actin filaments. Under physiological conditions, the N-BAR protein Bin1 has been shown to sense and curve membranes in a variety of cellular processes. Recent studies have identified Bin1 as a risk factor for Alzheimer's disease, although its possible pathological function in neurodegeneration is currently unknown. Here, we report that Bin1 not only shapes membranes, but is also directly involved in actin binding through its BAR domain. We observed a moderate actin bundling activity by human Bin1 and describe its ability to stabilize actin filaments against depolymerization. Moreover, Bin1 is also involved in stabilizing tau-induced actin bundles, which are neuropathological hallmarks of Alzheimer's disease. We also provide evidence for this effect in vivo, where we observed that downregulation of Bin1 in a Drosophila model of tauopathy significantly reduces the appearance of tau-induced actin inclusions. Together, these findings reveal the ability of Bin1 to modify actin dynamics and provide a possible mechanistic connection between Bin1 and tau-induced pathobiological changes of the actin cytoskeleton.
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BIN1 physically interacts with FAK, binds F-actin and CLIP170 in non-neuronal cells, and directly remodels actin dynamics through its BAR domain.
“BIN1 physically interacts with FA kinase (FAK), which presents strong homology with Pyk2 [90]. In addition, BIN1 binds to F-actin and microtubule-binding protein CLIP170 in non-neuronal cells [21] and directly remodels actin dynamics through its BAR domain [27].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [27]
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Cites
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Tau co-organizes dynamic microtubule and actin networks
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“…A b [26,27]. hBin1 can directly bind tau via its SH3 domain and the Bin1-tau complexes colocalize with the actin cytoskeleton in primary neurons [21,59]. dBin1 modulates tau-induced neurotoxicity in Drosophila [21,28], while in human cell culture studies, downregulation of hBin1 promotes tau…”
BIN1 regulates BACE1 intracellular trafficking and amyloid-β production
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SH3 domain‐dependent interactions of endophilin with amphiphysin
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Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors
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Structural Basis of Tau Interaction With BIN1 and Regulation by Tau Phosphorylation
Lasorsa, A., Malki, I., Cantrelle, F.-X., Merzougui, H., Boll, E., Lambert, J.-C., & Landrieu, I. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00421 · Cited by 58 · see citing works
- Authors
- Dräger, N. M., Nachman, E., Winterhoff, M., Brühmann, S., Shah, P., Katsinelos, T., Boulant, S., Teleman, A. A., Faix, J., & Jahn, T. R.
- Affiliations
- German Cancer Research Center (DE)
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Jahn, Thomas R
- ORCID
- Venue
- The EMBO Reports
- Published
- 2017-09-11
- Volume
- 18
- Issue
- 11
- Pages
- 2051-2066
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC5666605
- OpenAlex
- W2751660345
- Cited by
- 51
- References
- 9
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 6
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- EMBO Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chica and Heinz Schaller Foundation
- Deutsche Forschungsgemeinschaft (FA33010/1)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- BIN1, BAR domain, actin dynamics, actin cytoskeleton, tauopathy, actin cytoskeleton remodeling
- MeSH terms
- Actins, Animals, Binding Sites, Carrier Proteins, Cloning, Molecular, Disease Models, Animal, Drosophila melanogaster, Escherichia coli, Gene Expression Regulation, Genetic Vectors, Humans, Actin Cytoskeleton, Nuclear Proteins, Protein Binding, Recombinant Proteins, Transcription Factors, Gene Expression, tau Proteins, Protein Isoforms, Tauopathies, Tumor Suppressor Proteins, Drosophila Proteins, Adaptor Proteins, Signal Transducing, Protein Interaction Domains and Motifs
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