TY  - JOUR
AU  - Hofmann, Julia P
AU  - Denner, Philip
AU  - Nussbaum-Krammer, Carmen
AU  - Kuhn, Peer-Hendrik
AU  - Suhre, Michael H
AU  - Scheibel, Thomas
AU  - Lichtenthaler, Stefan F
AU  - Schätzl, Hermann M
AU  - Bano, Daniele
AU  - Vorberg, Ina M
TI  - Cell-to-cell propagation of infectious cytosolic protein aggregates.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 110
IS  - 15
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DZNE-2020-03196
SP  - 5951-5956
PY  - 2013
AB  - Prions are self-templating protein conformers that replicate by recruitment and conversion of homotypic proteins into growing protein aggregates. Originally identified as causative agents of transmissible spongiform encephalopathies, increasing evidence now suggests that prion-like phenomena are more common in nature than previously anticipated. In contrast to fungal prions that replicate in the cytoplasm, propagation of mammalian prions derived from the precursor protein PrP is confined to the cell membrane or endocytic vesicles. Here we demonstrate that cytosolic protein aggregates can also behave as infectious entities in mammalian cells. When expressed in the mammalian cytosol, protein aggregates derived from the prion domain NM of yeast translation termination factor Sup35 persistently propagate and invade neighboring cells, thereby inducing a self-perpetuating aggregation state of NM. Cell contact is required for efficient infection. Aggregates can also be induced in primary astrocytes, neurons, and organotypic cultures, demonstrating that this phenomenon is not specific to immortalized cells. Our data have important implications for understanding prion-like phenomena of protein aggregates associated with human diseases and for the growing number of amyloidogenic proteins discovered in mammals.
KW  - Animals
KW  - Astrocytes: cytology
KW  - Cell Communication
KW  - Coculture Techniques
KW  - Cytoplasm: metabolism
KW  - Cytosol: metabolism
KW  - Green Fluorescent Proteins: metabolism
KW  - Hippocampus: metabolism
KW  - Mice
KW  - Microscopy, Confocal
KW  - Peptide Termination Factors: metabolism
KW  - Prion Diseases
KW  - Prions: metabolism
KW  - Protein Conformation
KW  - Saccharomyces cerevisiae: metabolism
KW  - Saccharomyces cerevisiae Proteins: metabolism
KW  - Peptide Termination Factors (NLM Chemicals)
KW  - Prions (NLM Chemicals)
KW  - SUP35 protein, S cerevisiae (NLM Chemicals)
KW  - Saccharomyces cerevisiae Proteins (NLM Chemicals)
KW  - Green Fluorescent Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:23509289
C2  - pmc:PMC3625284
DO  - DOI:10.1073/pnas.1217321110
UR  - https://pub.dzne.de/record/136874
ER  -