Research article - Peer-reviewed, 2012
Separate mechanisms act concurrently to shed and release the prion protein from the cell
Wik, Lotta; Klingeborn, Mikael; Willander, Hanna; Linne, TommyAbstract
The cellular prion protein (PrPC) is attached to the cell membrane via its glycosylphosphatidylinositol (GPI)-anchor and is constitutively shed into the extracellular space. Here, three different mechanisms are presented that concurrently shed PrPC from the cell. The fast alpha-cleavage released a N-terminal fragment (N1) into the medium and the extreme C-terminal cleavage shed soluble full-length (FL-S) PrP and C-terminally cleaved (C1-S) fragments outside the cell. Also, a slow exosomal release of full-length (FL) and C1-fragment (C1) was demonstrated. The three separate mechanisms acting simultaneously, but with different kinetics, have to be taken into consideration when elucidating functional roles of PrPC and also when processing of PrPC is considered as a target for intervention in prion diseases. Further, in this study it was shown that metalloprotease inhibitors affected the extreme C-terminal cleavage and shedding of PrPC. The metalloprotease inhibitors did not influence the alpha-cleavage or the exosomal release. Taken together, these results are important for understanding the different mechanisms acting in parallel in the shedding and cleavage of PrPC.Keywords
prion; exosomes; shedding; alpha-cleavage; extreme C-terminal cleavage; inhibitorPublished in
Prion2012, volume: 6, number: 5
Publisher: LANDES BIOSCIENCE
Authors' information
Wik, Lotta
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
Klingeborn, Mikael
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
Willander, Hanna
Karolinska Institute
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
UKÄ Subject classification
Biochemistry and Molecular Biology
Publication Identifiers
DOI: https://doi.org/10.4161/pri.22588
URI (permanent link to this page)
https://res.slu.se/id/publ/44833