Prion protein conversion at two distinct cellular sites precedes fibrillisation

Juan Manuel Ribes, Mitali P. Patel, Hazim A. Halim, Antonio Berretta, Sharon A. Tooze and Peter-Christian Klöhn ()
Additional contact information
Juan Manuel Ribes: University College London
Mitali P. Patel: University College London
Hazim A. Halim: University College London
Antonio Berretta: University College London
Sharon A. Tooze: the Francis Crick Institute
Peter-Christian Klöhn: University College London

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract The self-templating nature of prions plays a central role in prion pathogenesis and is associated with infectivity and transmissibility. Since propagation of proteopathic seeds has now been acknowledged a principal pathogenic process in many types of dementia, more insight into the molecular mechanism of prion replication is vital to delineate specific and common disease pathways. By employing highly discriminatory anti-PrP antibodies and conversion-tolerant PrP chimera, we here report that de novo PrP conversion and formation of fibril-like PrP aggregates are distinct in mechanistic and kinetic terms. De novo PrP conversion occurs within minutes after infection at two subcellular locations, while fibril-like PrP aggregates are formed exclusively at the plasma membrane, hours after infection. Phenotypically distinct pools of abnormal PrP at perinuclear sites and the plasma membrane show differences in N-terminal processing, aggregation state and fibril formation and are linked by exocytic transport via synaptic and large-dense core vesicles.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-43961-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43961-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-43961-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().