Fibril-induced glutamine-/asparagine-rich prions recruit stress granule proteins in mammalian cells

Prions of lower eukaryotes are self-templating protein aggregates that replicate by converting homotypic proteins into stable, tightly packed beta-sheet-rich protein assemblies. Propagation is mediated by prion domains, low-complexity regions enriched in polar and devoid of charged amino acid residu...

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Bibliographic Details
Published in:Life science alliance 2019-08, Vol.2 (4), p.e201800280
Main Authors: Riemschoss, Katrin, Arndt, Verena, Bolognesi, Benedetta, von Eisenhart-Rothe, Philipp, Liu, Shu, Buravlova, Oleksandra, Duernberger, Yvonne, Paulsen, Lydia, Hornberger, Annika, Hossinger, André, Lorenzo-Gotor, Nieves, Hogl, Sebastian, Müller, Stephan A, Tartaglia, Gian, Lichtenthaler, Stefan F, Vorberg, Ina M
Format: Article
Language:English
Subjects:
Animals
Asparagine
Cell Line, Tumor
Cytoplasmic Granules - metabolism
Cytoskeleton - metabolism
DNA-Binding Proteins - metabolism
Gene Ontology
Glutamine
Mice
Peptide Termination Factors - chemistry
Peptide Termination Factors - metabolism
Prions - chemistry
Prions - metabolism
Protein Domains
Proteolysis
RNA-Binding Proteins - metabolism
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - metabolism
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Summary:Prions of lower eukaryotes are self-templating protein aggregates that replicate by converting homotypic proteins into stable, tightly packed beta-sheet-rich protein assemblies. Propagation is mediated by prion domains, low-complexity regions enriched in polar and devoid of charged amino acid residues. In mammals, compositionally similar domains modulate the assembly of dynamic stress granules (SGs) that associate via multivalent weak interactions. Dysregulation of SGs composed of proteins with prion-like domains has been proposed to underlie the formation of pathological inclusions in several neurodegenerative diseases. The events that drive prion-like domains into transient or solid assemblies are not well understood. We studied the interactors of the prototype prion domain NM of Sup35 in its soluble or fibril-induced prion conformation in the mammalian cytosol. We show that the interactomes of soluble and prionized NM overlap with that of SGs. Prion induction by exogenous seeds does not cause SG assembly, demonstrating that colocalization of aberrant protein inclusions with SG components does not necessarily reveal SGs as initial sites of protein misfolding.
ISSN:2575-1077
2575-1077
DOI:10.26508/lsa.201800280