Bin1 directly remodels actin dynamics through its BAR domain
Autor: | Steeve Boulant, Nina M. Dräger, Stefan Brühmann, Pranav N.M. Shah, Eliana Nachman, Aurelio A. Teleman, Jan Faix, Taxiarchis Katsinelos, Thomas R. Jahn, Moritz Winterhoff |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Genetic Vectors Gene Expression Arp2/3 complex tau Proteins macromolecular substances Biology Biochemistry 03 medical and health sciences Actin remodeling of neurons Escherichia coli Genetics Animals Drosophila Proteins Humans Protein Isoforms Protein Interaction Domains and Motifs Actin-binding protein Cloning Molecular Molecular Biology Adaptor Proteins Signal Transducing Binding Sites Tumor Suppressor Proteins Nuclear Proteins Actin remodeling Articles Actin cytoskeleton Actins Recombinant Proteins Cell biology Actin Cytoskeleton Disease Models Animal Drosophila melanogaster 030104 developmental biology Gene Expression Regulation Tauopathies Profilin biology.protein MDia1 Lamellipodium Carrier Proteins Protein Binding Transcription Factors |
Zdroj: | EMBO reports. 18:2051-2066 |
ISSN: | 1469-3178 1469-221X |
Popis: | 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. |
Databáze: | OpenAIRE |
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