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    题名: Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor
    作者: Dipak K. Giri;Mohamed Ali-Seyed;Long-Yuan Li;Dung-Fang Lee;Pin Ling;Geoffrey Bartholomeusz;Shao-Chun Wang;Mien-Chie Hung
    日期: 2005-12
    上传时间: 2009-11-27 13:57:02 (UTC+8)
    出版者: Asia University
    摘要: 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 ?1, nuclear pore protein Nup358, and a host of players in endocytic internalization. Knocking down importin ?1 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 ?1 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 ?1 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.
    關聯: MOLECULAR AND CELLULAR BIOLOGY 24(25):11005-11018
    显示于类别:[生物科技學系] 期刊論文

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