Separate mechanisms act concurrently to shed and release the prion protein from the cell
| Autor: | Hanna Willander, Tommy Linné, Mikael Klingeborn, Lotta Wik |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Prions
animal diseases Cell Biology Exosomes Cleavage (embryo) Biochemistry Cell Line Prion Diseases Cell membrane Cellular and Molecular Neuroscience Cricetinae mental disorders Extracellular medicine Animals PrPC Proteins Prion protein Metalloproteinase Cell Membrane Cell Biology Microvesicles nervous system diseases Cell biology Kinetics Infectious Diseases medicine.anatomical_structure Cell culture Metalloproteases Research Paper |
| Zdroj: | Prion. 6:498-509 |
| ISSN: | 1933-690X 1933-6896 |
| Popis: | The cellular prion protein (PrP (C) ) 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 PrP (C) from the cell. The fast α-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 PrP (C) and also when processing of PrP (C) 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 PrP (C) . The metalloprotease inhibitors did not influence the α-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 PrP (C) . |
| Databáze: | OpenAIRE |
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