Nuclear aggregation of polyglutamine-expanded ataxin-3: fragments escape the cytoplasmic quality control.

ABSTRACT: Expansion of a polymorphic polyglutamine segment is the common denominator of neurodegenerative polyglutamine diseases. The expanded proteins typically accumulate in large intranuclear inclusions and induce neurodegeneration. However, the mechanisms that determine the subcellular site and rate of inclusion formation are largely unknown. We found that the conserved putative nuclear localization sequence Arg-Lys-Arg-Arg, which is retained in a highly aggregation-prone fragment of ataxin-3, did not affect the site and degree of inclusion formation in a cell culture model of spinocerebellar ataxia type 3. Addition of synthetic nuclear export or import signals led to the expected localization of ataxin-3 and determined the subcellular site of aggregate formation. Triggering a cellular stress re

SUBMITTER: Breuer P 

PROVIDER: S-EPMC2825449 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature