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Bin1 directly remodels actin dynamics through its BAR domain
Author(s) -
Dräger Nina M,
Nachman Eliana,
Winterhoff Moritz,
Brühmann Stefan,
Shah Pranav,
Katsinelos Taxiarchis,
Boulant Steeve,
Teleman Aurelio A,
Faix Jan,
Jahn Thomas R
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744137
Subject(s) - actin , domain (mathematical analysis) , microbiology and biotechnology , dynamics (music) , bar (unit) , biophysics , physics , chemistry , biology , mathematics , meteorology , mathematical analysis , acoustics
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.