Polarised asymmetric inheritance of accumulated protein damage in higher eukaryotes.
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.
Rujano
María A
MA
Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Bosveld
Floris
F
Salomons
Florian A
FA
Dijk
Freark
F
van Waarde
Maria A W H
MA
van der Want
Johannes J L
JJ
de Vos
Rob A I
RA
Brunt
Ewout R
ER
Sibon
Ody C M
OC
Kampinga
Harm H
HH
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*
D011506:Proteins; D011099:Polyglutamic Acid