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Life Sci Alliance. 2019 Jul 2;2(4). pii: e201800280. doi: 10.26508/lsa.201800280. Print 2019 Aug.

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

Author information

1
German Center for Neurodegenerative Diseases Bonn (DZNE e.V.), Bonn, Germany.
2
Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona, Spain.
3
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
4
Neuroproteomics, School of Medicine, Klinikum rechts der Isar, and Institute for Advanced Study, Technical University of Munich, Munich, Germany.
5
Universitat Pompeu Fabra, Barcelona, Spain.
6
Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
7
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
8
German Center for Neurodegenerative Diseases Bonn (DZNE e.V.), Bonn, Germany ina.vorberg@dzne.de.
9
Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.

Abstract

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 Saccharomyces cerevisiae 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.

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