Cytoplasmic dynein/dynactin mediates the assembly of aggresomes.
Cell Motil Cytoskeleton
; 53(1): 26-38, 2002 Sep.
Article
em En
| MEDLINE
| ID: mdl-12211113
ABSTRACT
Aggresomes are pericentrosomal cytoplasmic structures into which aggregated, ubiquitinated, misfolded proteins are sequestered. Misfolded proteins accumulate in aggresomes when the capacity of the intracellular protein degradation machinery is exceeded. Previously, we demonstrated that an intact microtubule cytoskeleton is required for the aggresome formation [Johnston et al., 1998 J. Cell Biol. 1431883-1898]. In this study, we have investigated the involvement of microtubules (MT) and MT motors in this process. Induction of aggresomes containing misfolded DeltaF508 CFTR is accompanied by a redistribution of the retrograde motor cytoplasmic dynein that colocalizes with aggresomal markers. Coexpression of the p50 (dynamitin) subunit of the dynein/dynactin complex prevents the formation of aggresomes, even in the presence of proteasome inhibitors. Using in vitro microtubule binding assays in conjunction with immunogold electron microscopy, our data demonstrate that misfolded DeltaF508 CFTR associate with microtubules. We conclude that cytoplasmic dynein/dynactin is responsible for the directed transport of misfolded protein into aggresomes. The implications of these findings with respect to the pathogenesis of neurodegenerative disease are discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Organelas
/
Corpos de Inclusão
/
Dobramento de Proteína
/
Proteínas Motores Moleculares
/
Citoplasma
/
Células Eucarióticas
/
Microtúbulos
Limite:
Humans
Idioma:
En
Revista:
Cell Motil Cytoskeleton
Ano de publicação:
2002
Tipo de documento:
Article