Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor.
Mol Cell Biol
; 25(24): 11005-18, 2005 Dec.
Article
em En
| MEDLINE
| ID: mdl-16314522
ABSTRACT
The cell membrane receptor ErbB-2 migrates to the nucleus. However, the mechanism of its nuclear translocation is unclear. Here, we report a novel mechanism of its nuclear localization that involves interaction with the transport receptor importin beta1, nuclear pore protein Nup358, and a host of players in endocytic internalization. Knocking down importin beta1 using small interfering RNA oligonucleotides or inactivation of small GTPase Ran by RanQ69L, a dominant-negative mutant of Ran, causes a nuclear transport defect of ErbB-2. Mutation of a putative nuclear localization signal in ErbB-2 destroys its interaction with importin beta1 and arrests nuclear translocation, while inactivation of nuclear export receptor piles up ErbB-2 within the nucleus. Additionally, blocking of internalization by a dominant-negative mutant of dynamin halts its nuclear localization. Thus, the cell membrane-embedded ErbB-2, through endocytosis using the endocytic vesicle as a vehicle, importin beta1 as a driver and Nup358 as a traffic light, migrates from the cell surface to the nucleus. This novel mechanism explains how a receptor tyrosine kinase on the cell surface can be translocated into the nucleus. This pathway may serve as a general mechanism to allow direct communication between cell surface receptors and the nucleus, and our findings thus open a new era in understanding direct trafficking between the cell membrane and nucleus.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Núcleo Celular
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Receptores de Superfície Celular
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Receptor ErbB-2
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Chaperonas Moleculares
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Beta Carioferinas
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Complexo de Proteínas Formadoras de Poros Nucleares
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Endocitose
Limite:
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article