Specific glycosaminoglycan chain length and sulfation patterns are required for cell uptake of tau versus (cid:2) -synuclein and (cid:3) -amyloid aggregates

Transcellular propagation of protein aggregate “seeds” has been proposed to mediate the progression of neurodegenerative diseases in tauopathies and (cid:2) -synucleinopathies. We previously reported that tau and (cid:2) -synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface, promoting cellular uptake and intracellular seeding. However, the specificity and binding mode of these protein aggregates to HSPGs remain unknown. Here, we measured direct interaction with modified heparins to determine the size and sulfation requirements for tau, (cid:2) -synuclein, and (cid:3) -amyloid (A (cid:3) ) aggregate binding to gly-cosaminoglycans(GAGs).VaryingtheGAGlengthandsulfation patterns, we next conducted competition studies with heparin derivatives in cell-based assays. Tau aggregates required a pre-cise

[1]  Xander M R van Wijk,et al.  Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type , 2017, Scientific Reports.

[2]  K. Kosik,et al.  Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs) , 2017, Scientific Reports.

[3]  David Lindenmayer,et al.  A subcellular map of the human proteome , 2017, Science.

[4]  R. Woods,et al.  Synthesis of 3-O-Sulfated Oligosaccharides to Understand the Relationship between Structures and Functions of Heparan Sulfate. , 2017, Journal of the American Chemical Society.

[5]  G. Lippens,et al.  Glycan Determinants of Heparin-Tau Interaction. , 2017, Biophysical journal.

[6]  Tuo Li,et al.  An Argonaute phosphorylation cycle promotes microRNA-mediated silencing , 2016, Nature.

[7]  M. Diamond,et al.  Tau Prion Strains Dictate Patterns of Cell Pathology, Progression Rate, and Regional Vulnerability In Vivo , 2016, Neuron.

[8]  R. Woods,et al.  Uncovering the Relationship between Sulphation Patterns and Conformation of Iduronic Acid in Heparan Sulphate , 2016, Scientific Reports.

[9]  M. Diamond,et al.  Sensitive Detection of Proteopathic Seeding Activity with FRET Flow Cytometry. , 2015, Journal of visualized experiments : JoVE.

[10]  G. von Heijne,et al.  Tissue-based map of the human proteome , 2015, Science.

[11]  B. van Steensel,et al.  Easy quantitative assessment of genome editing by sequence trace decomposition , 2014, Nucleic acids research.

[12]  N. J. Allen,et al.  The role of neuronal versus astrocyte-derived heparan sulfate proteoglycans in brain development and injury. , 2014, Biochemical Society transactions.

[13]  Nigel J. Cairns,et al.  Proteopathic tau seeding predicts tauopathy in vivo , 2014, Proceedings of the National Academy of Sciences.

[14]  Neville E. Sanjana,et al.  Improved vectors and genome-wide libraries for CRISPR screening , 2014, Nature Methods.

[15]  L. Grinberg,et al.  Distinct Tau Prion Strains Propagate in Cells and Mice and Define Different Tauopathies , 2014, Neuron.

[16]  J. Esko,et al.  Demystifying heparan sulfate-protein interactions. , 2014, Annual review of biochemistry.

[17]  M. Busse-Wicher,et al.  The exostosin family: proteins with many functions. , 2014, Matrix biology : journal of the International Society for Matrix Biology.

[18]  Amit Sharma,et al.  DNASU plasmid and PSI:Biology-Materials repositories: resources to accelerate biological research , 2013, Nucleic Acids Res..

[19]  K. Airenne,et al.  6-O- and N-Sulfated Syndecan-1 Promotes Baculovirus Binding and Entry into Mammalian Cells , 2013, Journal of Virology.

[20]  F. Brodsky,et al.  Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds , 2013, Proceedings of the National Academy of Sciences.

[21]  L. Kjellén,et al.  Pathophysiology of heparan sulphate: many diseases, few drugs , 2013, Journal of internal medicine.

[22]  G. Bu,et al.  Heparan Sulphate Proteoglycan and the Low-Density Lipoprotein Receptor-Related Protein 1 Constitute Major Pathways for Neuronal Amyloid-β Uptake , 2011, The Journal of Neuroscience.

[23]  K. Doh-ura,et al.  Continuous intraventricular infusion of pentosan polysulfate: Clinical trial against prion diseases , 2009, Neuropathology : official journal of the Japanese Society of Neuropathology.

[24]  Jeffrey D. Esko,et al.  Heparan sulphate proteoglycans fine-tune mammalian physiology , 2007, Nature.

[25]  L. Hsieh‐Wilson,et al.  Profiling the sulfation specificities of glycosaminoglycan interactions with growth factors and chemotactic proteins using microarrays. , 2007, Chemistry & biology.

[26]  B. Caughey,et al.  Uptake and Neuritic Transport of Scrapie Prion Protein Coincident with Infection of Neuronal Cells , 2022 .

[27]  Y. Yedidia,et al.  Heparan Sulfate Is a Cellular Receptor for Purified Infectious Prions* , 2005, Journal of Biological Chemistry.

[28]  J. Milbrandt,et al.  Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal Degeneration , 2004, Science.

[29]  T. Iwaki,et al.  Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models , 2004, Journal of Virology.

[30]  J. Esko,et al.  Cellular Heparan Sulfate Participates in the Metabolism of Prions* , 2003, Journal of Biological Chemistry.

[31]  T. Wight,et al.  Perlecan Binds to the β‐Amyloid Proteins (Aβ) of Alzheimer's Disease, Accelerates Aβ Fibril Formation, and Maintains Aβ Fibril Stability , 1997 .

[32]  R. Crowther,et al.  Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans , 1996, Nature.

[33]  G. J. Raymond,et al.  Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells , 1993, Journal of virology.

[34]  J. Massagué,et al.  A single mutation affects both N-acetylglucosaminyltransferase and glucuronosyltransferase activities in a Chinese hamster ovary cell mutant defective in heparan sulfate biosynthesis. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[35]  B. Ehlers,et al.  Chemoprophylaxis of scrapie in mice. , 1991, The Journal of general virology.