siRNA-mediated inhibition of endogenous Huntington disease gene expression induces an aberrant configuration of the ER network in vitro.
Biochem Biophys Res Commun
; 338(2): 1229-35, 2005 Dec 16.
Article
en En
| MEDLINE
| ID: mdl-16256944
ABSTRACT
Huntingtin is a ubiquitously expressed cytoplasmic protein encoded by the Huntington disease (HD) gene, in which a CAG expansion induces an autosomal dominant progressive neurodegenerative disorder; however, its biological function has not been completely elucidated. Here, we report for the first time that short interfering RNA (siRNA)-mediated inhibition of endogenous Hdh (a mouse homologue of huntingtin) gene expression induced an aberrant configuration of the endoplasmic reticulum (ER) network in vitro. Studies using immunofluorescence microscopy with several ER markers revealed that the ER network appeared to be congregated in various types of cell lines transfected with siRNA directed against Hdh, but not with other siRNAs so far tested. Other subcellular organelles and structures, including the nucleus, Golgi apparatus, mitochondria, lysosomes, microtubules, actin cytoskeletons, cytoplasm, lipid rafts, and plasma membrane, exhibited normal configurations. Western blot analysis of cellular prion protein (PrP(C)) revealed normal glycosylation, which is a simple marker of post-translational modification in the ER and Golgi compartments, and immunofluorescence microscopy detected no altered subcellular distribution of PrP(C) in the post-ER compartments. Further investigation is required to determine whether the distorted ER network, i.e., loss of the huntingtin function, participates in the development of HD.
Buscar en Google
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Retículo Endoplásmico
/
Proteínas del Tejido Nervioso
/
Neuronas
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2005
Tipo del documento:
Article
País de afiliación:
Japón