Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor.

Article Details

Citation

Giri DK, Ali-Seyed M, Li LY, Lee DF, Ling P, Bartholomeusz G, Wang SC, Hung MC

Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor.

Mol Cell Biol. 2005 Dec;25(24):11005-18.

PubMed ID
16314522 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Receptor tyrosine-protein kinase erbB-2P04626Details
Early endosome antigen 1Q15075Details