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

Dipak K. Giri, Mohamed Ali-Seyed, Long Yuan Li, Dung Fang Lee, Pin Ling, Geoffrey Bartholomeusz, Shao Chun Wang, Mien Chie Hung

Research output: Contribution to journalArticle

159 Citations (Scopus)

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 β1, nuclear pore protein Nup358, and a host of players in endocytic internalization. Knocking down importin β1 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 β1 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 β1 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.

Original languageEnglish
Pages (from-to)11005-11018
Number of pages14
JournalMolecular and Cellular Biology
Volume25
Issue number24
DOIs
Publication statusPublished - 2005 Dec 1

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Karyopherins
Cell Surface Receptors
Cell Nucleus Active Transport
Cell Membrane
ErbB-2 Receptor
Dynamins
Nuclear Pore
Transport Vesicles
Nuclear Localization Signals
Porins
Monomeric GTP-Binding Proteins
Receptor Protein-Tyrosine Kinases
Cytoplasmic and Nuclear Receptors
Nuclear Proteins
Endocytosis
Cell Nucleus
Oligonucleotides
Small Interfering RNA
Light
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Giri, D. K., Ali-Seyed, M., Li, L. Y., Lee, D. F., Ling, P., Bartholomeusz, G., ... Hung, M. C. (2005). Endosomal transport of ErbB-2: Mechanism for nuclear entry of the cell surface receptor. Molecular and Cellular Biology, 25(24), 11005-11018. https://doi.org/10.1128/MCB.25.24.11005-11018.2005
Giri, Dipak K. ; Ali-Seyed, Mohamed ; Li, Long Yuan ; Lee, Dung Fang ; Ling, Pin ; Bartholomeusz, Geoffrey ; Wang, Shao Chun ; Hung, Mien Chie. / Endosomal transport of ErbB-2 : Mechanism for nuclear entry of the cell surface receptor. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 24. pp. 11005-11018.
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Giri, DK, Ali-Seyed, M, Li, LY, Lee, DF, Ling, P, Bartholomeusz, G, Wang, SC & Hung, MC 2005, 'Endosomal transport of ErbB-2: Mechanism for nuclear entry of the cell surface receptor', Molecular and Cellular Biology, vol. 25, no. 24, pp. 11005-11018. https://doi.org/10.1128/MCB.25.24.11005-11018.2005

Endosomal transport of ErbB-2 : Mechanism for nuclear entry of the cell surface receptor. / Giri, Dipak K.; Ali-Seyed, Mohamed; Li, Long Yuan; Lee, Dung Fang; Ling, Pin; Bartholomeusz, Geoffrey; Wang, Shao Chun; Hung, Mien Chie.

In: Molecular and Cellular Biology, Vol. 25, No. 24, 01.12.2005, p. 11005-11018.

Research output: Contribution to journalArticle

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T2 - Mechanism for nuclear entry of the cell surface receptor

AU - Giri, Dipak K.

AU - Ali-Seyed, Mohamed

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AU - Lee, Dung Fang

AU - Ling, Pin

AU - Bartholomeusz, Geoffrey

AU - Wang, Shao Chun

AU - Hung, Mien Chie

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