Journal Article

DZNE-2020-03196

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cell-to-cell propagation of infectious cytosolic protein aggregates.

Hofmann, J. P. (First author)DZNE* ; Denner, P.DZNE* ; Nussbaum-Krammer, C. ; Kuhn, P.-H.DZNE* ; Suhre, M. H. ; Scheibel, T. ; Lichtenthaler, S. F.DZNE* ; Schätzl, H. M. ; Bano, D.DZNE* ; Vorberg, I. M. (Last author)DZNE*

2013
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.1217321110

Abstract: 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.

Keyword(s): Animals (MeSH) ; Astrocytes: cytology (MeSH) ; Cell Communication (MeSH) ; Coculture Techniques (MeSH) ; Cytoplasm: metabolism (MeSH) ; Cytosol: metabolism (MeSH) ; Green Fluorescent Proteins: metabolism (MeSH) ; Hippocampus: metabolism (MeSH) ; Mice (MeSH) ; Microscopy, Confocal (MeSH) ; Peptide Termination Factors: metabolism (MeSH) ; Prion Diseases (MeSH) ; Prions: metabolism (MeSH) ; Protein Conformation (MeSH) ; Saccharomyces cerevisiae: metabolism (MeSH) ; Saccharomyces cerevisiae Proteins: metabolism (MeSH) ; Peptide Termination Factors ; Prions ; SUP35 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Green Fluorescent Proteins

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Contributing Institute(s):

1. Neuroproteomics (AG Lichtenthaler)
2. Aging and neurodegeneration (AG Bano)
3. Nuclear function in CNS pathophysiology (AG Salomoni)
4. Prion Cell Biology (AG Vorberg)
5. Laboratory Automation Technologies (LAT) (LAT)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Experiment(s):

1. Laboratory Automation Technologies (CRFS-LAT) / Bonn

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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