title: Cytosolic and nuclear aggregation of the amyloid beta-peptide following its expression in the endoplasmic reticulum.
abstract: Misfolded secretory and membrane proteins are known to be exported from the endoplasmic reticulum (ER) to the cytosol where they are degraded by proteasomes. When the amount of exported misfolded proteins exceeds the capacity of this degradation mechanism the proteins accumulate in the form of pericentriolar aggregates called aggresomes. Here, we show that the amyloid beta-peptide (Abeta) forms cytosolic aggregates after its export from the ER. These aggregates share several constituents with aggresomes. However, Abeta aggregates are distinct from aggresomes in that they do not accumulate around the centrosome but are distributed randomly around the nucleus. In addition to these cytosolic aggregates, Abeta forms intranuclear aggregates which have as yet not been found for proteins exported from the ER. These findings show that proteins exported from the ER to the cytosol which escape degradation by the proteasome are not necessarily incorporated into aggresomes. We conclude that several distinct aggregation pathways may exist for proteins exported from the ER to the cytosol.
authors.affiliation: Institut für Zellbiologie, Rheinische-Friedrich-Wilhelms-Universität, Ulrich-Haberland-Strasse 61a, 53121 Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bückig
authors.forename: Ritva
authors.initials: R
authors.lastname: Tikkanen
authors.forename: Volker
authors.initials: V
authors.lastname: Herzog
authors.forename: Anton
authors.initials: A
authors.lastname: Schmitz
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001693:Biological Transport, Active; D016466:CHO Cells; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015853:Cysteine Proteinase Inhibitors; D025801:Ubiquitin; C067713:lactacystin; D000111:Acetylcysteine