RT Journal Article
SR Electronic
T1 Fibril-induced glutamine-/asparagine-rich prions recruit stress granule proteins in mammalian cells
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800280
DO 10.26508/lsa.201800280
VO 2
IS 4
A1 Riemschoss, Katrin
A1 Arndt, Verena
A1 Bolognesi, Benedetta
A1 von Eisenhart-Rothe, Philipp
A1 Liu, Shu
A1 Buravlova, Oleksandra
A1 Duernberger, Yvonne
A1 Paulsen, Lydia
A1 Hornberger, Annika
A1 Hossinger, André
A1 Lorenzo-Gotor, Nieves
A1 Hogl, Sebastian
A1 Müller, Stephan A
A1 Tartaglia, Gian
A1 Lichtenthaler, Stefan F
A1 Vorberg, Ina M
YR 2019
UL http://www.life-science-alliance.org/content/2/4/e201800280.abstract
AB 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.