COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport.
COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport.
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DOI：
10.1016/j.bbrc.2010.07.096
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发表时间：
2010-09-03
影响因子：
3.1
通讯作者：
Hung, Mien-Chie
中科院分区：
文献类型：
--
作者：
Wang, Ying-Nai;Wang, Hongmei;Yamaguchi, Hirohito;Lee, Hong-Jen;Lee, Heng-Huan;Hung, Mien-Chie
关键词：
新的证据表明，细胞表面受体，如整个表皮生长因子受体(EGFR)家族，已被证明定位于细胞核。一条从高尔基体到内质网(ER)的逆行途径被认为参与了EGFR向细胞核的运输；然而，在这个提出的模型中，分子机制仍然没有被探索。在这里，我们证明了膜包埋的囊泡运输参与了EGFR的核运输。共聚焦免疫荧光显示，作为对EGF的反应，EGFR的一部分重新分布到高尔基体和内质网，其NH2末端位于高尔基体/ER的管腔内，COOH末端暴露在细胞质中。Brefield din A或小GTP酶ADP-核糖化因子的显性突变体阻断高尔基体到内质网的逆行转运，两者都导致外壳蛋白复合体I(COPI)被解体到高尔基体，抑制EGFR向内质网和细胞核的转运。我们进一步发现，EGFR依赖于表皮生长因子的核运输是由从高尔基体到内质网的逆行运输调节的，涉及EGFR与γ-COP的关联，COP是COPI辅助体的一个亚单位。我们的发现从实验上提供了一条全面的途径，即EGFR的核运输受到COPI介导的囊泡从高尔基体到内质网的运输的调节，并可能作为调节其他细胞表面受体的核运输的一般机制。
Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored. Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH2-terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with γ-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.
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DOI：
10.1006/bbrc.1998.9790
发表时间：
1999-03-05
影响因子：
3.1
作者：
Feng, YY;Venema, VJ;Caldwell, RB
通讯作者：
Caldwell, RB
影响因子：
21.3
作者：
Lin, SY;Makino, K;Hung, MC
通讯作者：
Hung, MC
影响因子：
78.5
作者：
Massie, C;Mills, IG
通讯作者：
Mills, IG
影响因子：
5.3
作者：
Giri, DK;Ali-Seyed, M;Hung, MC
通讯作者：
Hung, MC
影响因子：
7.8
作者：
Crisp, M;Liu, Q;Hodzic, D
通讯作者：
Hodzic, D