Contribution of syndecans to cellular uptake and fibrillation of α-synuclein and tau
| Autor: | Katalin Jósvay, Ildikó Domonkos, Martin Hofmann-Apitius, Alpha Tom Kodamullil, László Szilák, Tamás Letoha, Anett Hudák, Erzsébet Kusz |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
animal structures Syndecans media_common.quotation_subject Endocytic cycle Protein domain Glycobiology lcsh:Medicine tau Proteins Protein aggregation Fibril Endocytosis Article Syndecan 1 03 medical and health sciences 0302 clinical medicine Protein Domains mental disorders medicine Humans Internalization lcsh:Science media_common Protein translocation Multidisciplinary Chemistry Neurodegeneration lcsh:R Membrane Proteins medicine.disease Cell biology nervous system diseases carbohydrates (lipids) 030104 developmental biology embryonic structures alpha-Synuclein lcsh:Q K562 Cells 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-19 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Scientific evidence suggests that α-synuclein and tau have prion-like properties and that prion-like spreading and seeding of misfolded protein aggregates constitutes a central mechanism for neurodegeneration. Heparan sulfate proteoglycans (HSPGs) in the plasma membrane support this process by attaching misfolded protein fibrils. Despite of intense studies, contribution of specific HSPGs to seeding and spreading of α-synuclein and tau has not been explored yet. Here we report that members of the syndecan family of HSPGs mediate cellular uptake of α-synuclein and tau fibrils via a lipid-raft dependent and clathrin-independent endocytic route. Among syndecans, the neuron predominant syndecan-3 exhibits the highest affinity for both α-synuclein and tau. Syndecan-mediated internalization of α-synuclein and tau depends heavily on conformation as uptake via syndecans start to dominate once fibrils are formed. Overexpression of syndecans, on the other hand, reduces cellular uptake of monomeric α-synuclein and tau, yet exerts a fibril forming effect on both proteins. Data obtained from syndecan overexpressing cellular models presents syndecans, especially the neuron predominant syndecan-3, as important mediators of seeding and spreading of α-synuclein and tau and reveal how syndecans contribute to fundamental molecular events of α-synuclein and tau pathology. |
| Databáze: | OpenAIRE |
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