3-O-sulfation of Heparan Sulfate Enhances Tau Interaction and Cellular Uptake
Authors
Zhao, Jing
Zhu, Yanan
Song, Xuehong
Xiao, Yuanyuan
Su, Guowei
Liu, Xinyue
Wang, Zhangjie
Xu, Yongmei
Liu, Jian
Eliezer, David
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2020-01-27
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
3-O-sulfation of Heparan Sulfate Enhances Tau Interaction and Cellular Uptake, J. Zhao, Y. Zhu, X. Song, Y. Xiao, G. Su, X. Liu, Z. Wang, Y. Xu, J. Liu, D. Eliezer, T. F. Ramlall, G. Lippens, J. Gibson, F. Zhang, R. J. Linhardt, L. Wang, C. Wang, Angewandte Chemie Int. Ed., 59, 1818-1827, 2020.
Abstract
Prion-like transcellular spreading of tau in Alzheimer's Disease (AD) is mediated by tau binding to cell surface heparan sulfate (HS). However, the structural determinants for tau-HS interaction are not well understood. Microarray and SPR assays of structurally defined HS oligosaccharides show that a rare 3-O-sulfation (3-O-S) of HS significantly enhances tau binding. In Hs3st1-/- (HS 3-O-sulfotransferase-1 knockout) cells, reduced 3-O-S levels of HS diminished both cell surface binding and internalization of tau. In a cell culture, the addition of a 3-O-S HS 12-mer reduced both tau cell surface binding and cellular uptake. NMR titrations mapped 3-O-S binding sites to the microtubule binding repeat 2 (R2) and proline-rich region 2 (PRR2) of tau. Tau is only the seventh protein currently known to recognize HS 3-O-sulfation. Our work demonstrates that this rare 3-O-sulfation enhances tau-HS binding and likely the transcellular spread of tau, providing a novel target for disease-modifying treatment of AD and other tauopathies.
Description
Angewandte Chemie Int. Ed., 59, 1818-1827
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Wiley
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Angewandte Chemie - International Edition
https://harc.rpi.edu/
Rensselaer Polytechnic Institute, Troy, NY
Angewandte Chemie - International Edition
https://harc.rpi.edu/
Access
A full text version is available in DSpace@RPI