The Mrj co-chaperone mediates keratin turnover and prevents the formation of toxic inclusion bodies in trophoblast cells of the placenta.
Development
; 134(9): 1809-17, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17409114
ABSTRACT
Defects in protein-folding and -degradation machinery have been identified as a major cause of intracellular protein aggregation and of aggregation-associated diseases. In general, it remains unclear how these aggregates are harmful to normal cellular function. We demonstrate here that, in the developing placenta of the mouse, the absence of the Mrj (Dnajb6) co-chaperone prevents proteasome degradation of keratin 18 (K18; Krt18) intermediate filaments, resulting in the formation of keratin inclusion bodies. These inclusions in chorionic trophoblast cells prevent chorioallantoic attachment during placental development. We show further that keratin-deficient embryos undergo chorioallantoic attachment and that, by genetically reducing keratin expression in Mrj(-/-) conceptuses, chorioallantoic attachment was rescued. Therefore, the chorioallantoic attachment phenotype in Mrj mutants is not due to a deficiency of the normal keratin cytoskeleton, but rather is cytotoxicity caused by keratin aggregates that disrupt chorion trophoblast cell organization and function.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Placenta
/
Trofoblastos
/
Corpos de Inclusão
/
Chaperonas Moleculares
/
Proteínas de Choque Térmico HSP40
/
Queratinas
Limite:
Animals
Idioma:
En
Revista:
Development
Ano de publicação:
2007
Tipo de documento:
Article