Titel
Cytoskeleton-dependent clustering of membrane-bound prion protein on the cell surface
Autor*in
Xue Wen Ng
Departments of Biological Sciences and Chemistry and Centre for Bioimaging Sciences (CBIS), National University of Singapore (NUS)
Autor*in
Danqin Lu
Departments of Biological Sciences and Chemistry and Centre for Bioimaging Sciences (CBIS), National University of Singapore (NUS)
... show all
Abstract
Prion diseases are a group of neurodegenerative disorders that infect animals and humans with proteinaceous particles called prions. Prions consist of scrapie prion protein (PrPSc), a misfolded version of the cellular prion protein (PrPC). During disease progression, PrPSc replicates by interacting with PrPC and inducing its conversion to PrPSc. Attachment of PrPC to cellular membranes via a glycosylphosphatidylinositol (GPI) anchor is critical for the conversion of PrPC into PrPSc. However, the mechanisms governing PrPC conversion and replication on the membrane remain largely unclear. Here, a site-selectively modified PrP variant equipped with a fluorescent GPI anchor mimic (PrP-GPI) was employed to directly observe PrP at the cellular membrane in neuronal SH-SY5Y cells. PrP-GPI exhibits a cholesterol-dependent membrane accumulation and a cytoskeleton-dependent mobility. More specifically, inhibition of actin polymerization reduced the diffusion of PrP-GPI indicating protein clustering, which resembles the initial step of PrP aggregation and conversion into its pathogenic isoform. An intact actin cytoskeleton might therefore prevent conversion of PrPC into PrPSc and offer new therapeutic angles.
Stichwort
prion proteinprotein aggregationmembrane-associated proteinsmembrane biophysicscytoskeletonfluorescence correlation spectroscopyprotein semisynthesis
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:1612057
Erschienen in
Titel
Journal of Biological Chemistry
Band
296
ISSN
0021-9258
Erscheinungsdatum
2021
Verlag
Elsevier BV
Erscheinungsdatum
2021
Zugänglichkeit
Rechteangabe
© 2021 The Authors

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