Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates

被引：331

作者：

Ren, Pei-Hsien ^{[1
]}

Lauckner, Jane E. ^{[1
]}

Kachirskaia, Ioulia ^{[1
]}

Heuser, John E. ^{[3
]}

Melki, Ronald ^{[2
]}

Kopito, Ron R. ^{[1
]}

机构：

[1] Stanford Univ, Dept Biol, Stanford, CA 94035 USA

[2] CNRS, Lab Enzymol & Biochim Struct, F-91198 Gif Sur Yvette, France

[3] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA

来源：

NATURE CELL BIOLOGY | 2009年 / 11卷 / 02期

关键词：

PROTEIN MISFOLDING DISEASES; YEAST PRION; IN-VITRO; HUNTINGTIN; TOXICITY; PROPAGATION; MECHANISM; PEPTIDES; FIBRILS;

D O I：

10.1038/ncb1830

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Sequence-specific nucleated protein aggregation is closely linked to the pathogenesis of most neurodegenerative diseases and constitutes the molecular basis of prion formation(1). 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.

引用

页码：219 / U232

页数：11

共 27 条

[1] Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases [J].