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.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Coat Protein Complex I / metabolism*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism*
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / metabolism*
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / metabolism*
  • Humans

Substances

  • Coat Protein Complex I
  • Epidermal Growth Factor
  • ErbB Receptors