COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport.

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Citation

Wang YN, Wang H, Yamaguchi H, Lee HJ, Lee HH, Hung MC

COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport.

Biochem Biophys Res Commun. 2010 Sep 3;399(4):498-504. doi: 10.1016/j.bbrc.2010.07.096. Epub 2010 Jul 30.

PubMed ID
20674546 [ View in PubMed
]
Abstract

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 NH(2)-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 gamma-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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Epidermal growth factor receptorP00533Details
Coatomer subunit gamma-1Q9Y678Details