Format

Send to

Choose Destination
EMBO Rep. 2017 Nov;18(11):2051-2066. doi: 10.15252/embr.201744137. Epub 2017 Sep 11.

Bin1 directly remodels actin dynamics through its BAR domain.

Author information

1
Proteostasis in Neurodegenerative Disease (B180), Schaller Research Group at the University of Heidelberg and DKFZ, Heidelberg, Germany.
2
German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg, Germany.
3
Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany.
4
Schaller Research Group at CellNetworks, Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg, Germany.
5
Cellular polarity and viral infection (F140), German Cancer Research Center (DKFZ), Heidelberg, Germany.
6
Signal Transduction in Cancer and Metabolism (B140), German Cancer Research Center (DKFZ), Heidelberg, Germany.
7
Proteostasis in Neurodegenerative Disease (B180), Schaller Research Group at the University of Heidelberg and DKFZ, Heidelberg, Germany thomas.r.jahn@abbvie.com.

Abstract

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.

KEYWORDS:

Alzheimer's disease; N‐BAR protein Bin1; actin binding; genetic risk factor; tau

PMID:
28893863
PMCID:
PMC5666605
DOI:
10.15252/embr.201744137
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center