Cytoplasmic Penetration and Persistent Infection of Mammalian Cells by Polyglutamine Aggregates

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2009 Jan 20

PMID 19151706

Citations 231

Authors

Pei-Hsien Ren

Jane E Lauckner

Ioulia Kachirskaia

John E Heuser

Ronald Melki

Ron R Kopito

Affiliations

Soon will be listed here.

Abstract

Sequence-specific nucleated protein aggregation is closely linked to the pathogenesis of most neurodegenerative diseases and constitutes the molecular basis of prion formation. Here we report that fibrillar polyglutamine peptide aggregates can be internalized by mammalian cells in culture where they gain access to the cytosolic compartment and become co-sequestered in aggresomes together with components of the ubiquitin-proteasome system and cytoplasmic chaperones. Remarkably, these internalized fibrillar aggregates are able to selectively recruit soluble cytoplasmic proteins with which they share homologous but not heterologous amyloidogenic sequences, and to confer a heritable phenotype on cells expressing the homologous amyloidogenic protein from a chromosomal locus.

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