title: Polarised asymmetric inheritance of accumulated protein damage in higher eukaryotes.
abstract: Disease-associated misfolded proteins or proteins damaged due to cellular stress are generally disposed via the cellular protein quality-control system. However, under saturating conditions, misfolded proteins will aggregate. In higher eukaryotes, these aggregates can be transported to accumulate in aggresomes at the microtubule organizing center. The fate of cells that contain aggresomes is currently unknown. Here we report that cells that have formed aggresomes can undergo normal mitosis. As a result, the aggregated proteins are asymmetrically distributed to one of the daughter cells, leaving the other daughter free of accumulated protein damage. Using both epithelial crypts of the small intestine of patients with a protein folding disease and Drosophila melanogaster neural precursor cells as models, we found that the inheritance of protein aggregates during mitosis occurs with a fixed polarity indicative of a mechanism to preserve the long-lived progeny.
authors.affiliation: Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: María A
authors.initials: MA
authors.lastname: Rujano
authors.forename: Floris
authors.initials: F
authors.lastname: Bosveld
authors.forename: Florian A
authors.initials: FA
authors.lastname: Salomons
authors.forename: Freark
authors.initials: F
authors.lastname: Dijk
authors.forename: Maria A W H
authors.initials: MA
authors.lastname: van Waarde
authors.forename: Johannes J L
authors.initials: JJ
authors.lastname: van der Want
authors.forename: Rob A I
authors.initials: RA
authors.lastname: de Vos
authors.forename: Ewout R
authors.initials: ER
authors.lastname: Brunt
authors.forename: Ody C M
authors.initials: OC
authors.lastname: Sibon
authors.forename: Harm H
authors.initials: HH
authors.lastname: Kampinga
mesh_terms: D000818:Animals; D016764:Cell Polarity; D002478:Cells, Cultured; D006224:Cricetinae; D004331:Drosophila melanogaster; D005057:Eukaryotic Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D011099:Polyglutamic Acid / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins; D011099:Polyglutamic Acid