PMID- 20674546
OWN - NLM
STAT- MEDLINE
DCOM- 20101007
LR  - 20220408
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 399
IP  - 4
DP  - 2010 Sep 3
TI  - COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR 
      nuclear transport.
PG  - 498-504
LID - 10.1016/j.bbrc.2010.07.096 [doi]
AB  - 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.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Wang, Ying-Nai
AU  - Wang YN
AD  - Department of Molecular and Cellular Oncology, The University of Texas, M.D. 
      Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Wang, Hongmei
AU  - Wang H
FAU - Yamaguchi, Hirohito
AU  - Yamaguchi H
FAU - Lee, Hong-Jen
AU  - Lee HJ
FAU - Lee, Heng-Huan
AU  - Lee HH
FAU - Hung, Mien-Chie
AU  - Hung MC
LA  - eng
GR  - P01 CA099031-07/CA/NCI NIH HHS/United States
GR  - R01 CA109311/CA/NCI NIH HHS/United States
GR  - R01 109311/PHS HHS/United States
GR  - R01 CA109311-07/CA/NCI NIH HHS/United States
GR  - P01 099031/PHS HHS/United States
GR  - P01 CA099031/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100730
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Coat Protein Complex I)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Cell Line, Tumor
MH  - Cell Nucleus/metabolism
MH  - Coat Protein Complex I/*metabolism
MH  - Endoplasmic Reticulum/drug effects/*metabolism
MH  - Epidermal Growth Factor/pharmacology
MH  - ErbB Receptors/*metabolism
MH  - Golgi Apparatus/drug effects/*metabolism
MH  - Humans
PMC - PMC2935258
MID - NIHMS226597
EDAT- 2010/08/03 06:00
MHDA- 2010/10/12 06:00
PMCR- 2011/09/03
CRDT- 2010/08/03 06:00
PHST- 2010/06/30 00:00 [received]
PHST- 2010/07/25 00:00 [accepted]
PHST- 2010/08/03 06:00 [entrez]
PHST- 2010/08/03 06:00 [pubmed]
PHST- 2010/10/12 06:00 [medline]
PHST- 2011/09/03 00:00 [pmc-release]
AID - S0006-291X(10)01416-6 [pii]
AID - 10.1016/j.bbrc.2010.07.096 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2010 Sep 3;399(4):498-504. doi: 
      10.1016/j.bbrc.2010.07.096. Epub 2010 Jul 30.