Proc Natl Acad Sci U S A
Laboratoire de Génétique Moléculaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8541, Ecole Normale Supérieure, 46 Rue d'Ulm, 75230 Paris Cedex 05, France.
Published: June 2004
Aggregation of misfolded proteins is a characteristic of several neurodegenerative diseases. The huntingtin amino-terminal fragment with extended polyglutamine repeat forms aggregates closely associated with chaperones both in the cytoplasm and the nucleus. Because each cellular compartment contains distinct chaperones and because the molecular mechanisms controlling polyglutamine aggregation are largely unknown, we decided to investigate the influence of different cellular environments on the aggregation of this pathological protein. Here, we show that aggregation of a protein containing a polyglutamine stretch of pathological length is abolished when its expression is targeted to the endoplasmic reticulum. Once retrogradely transported outside the endoplasmic reticulum, the aggregation-prone polyglutamine-containing protein recovers its ability to aggregate. When expressed in the mitochondria, a protein containing 73 glutamines is entirely soluble, whereas the nucleocytosolic equivalent has an extremely high tendency to aggregate. Our data imply that polyglutamine aggregation is a property restricted to the nucleocytosolic compartment and suggest the existence of compartment-specific cofactors promoting or preventing aggregation of pathological proteins.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC470729 | PMC |
http://dx.doi.org/10.1073/pnas.0403015101 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.