PMID- 21917092
OWN - NLM
STAT- MEDLINE
DCOM- 20120604
LR  - 20211020
IS  - 1600-0854 (Electronic)
IS  - 1398-9219 (Print)
IS  - 1398-9219 (Linking)
VI  - 12
IP  - 12
DP  - 2011 Dec
TI  - Identification of a novel mono-leucine basolateral sorting motif within the 
      cytoplasmic domain of amphiregulin.
PG  - 1793-804
LID - 10.1111/j.1600-0854.2011.01282.x [doi]
AB  - Epithelial cells establish apical and basolateral (BL) membranes with distinct 
      protein and lipid compositions. To achieve this spatial asymmetry, the cell 
      utilizes a variety of mechanisms for differential sorting, delivery and retention 
      of cell surface proteins. The EGF receptor (EGFR) and its ligand, amphiregulin 
      (AREG), are transmembrane proteins delivered to the BL membrane in polarized 
      epithelial cells. Herein, we show that the cytoplasmic domain of AREG (ACD) 
      contains dominant BL sorting information; replacement of the cytoplasmic domain 
      of apically targeted nerve growth factor receptor with the ACD redirects the 
      chimera to the BL surface. Using sequential truncations and site-directed 
      mutagenesis of the ACD, we identify a novel BL sorting motif consisting of a 
      single leucine C-terminal to an acidic cluster (EEXXXL). In adaptor protein 
      (AP)-1B-deficient cells, newly synthesized AREG is initially delivered to the BL 
      surface as in AP-1B-expressing cells. However, in these AP-1B-deficient cells, 
      recycling of AREG back to the BL surface is compromised, leading to its 
      appearance at the apical surface. These results show that recycling, but not 
      delivery, of AREG to the BL surface is AP-1B dependent.
CI  - (c) 2011 John Wiley & Sons A/S.
FAU - Gephart, Jonathan D
AU  - Gephart JD
AD  - Department of Cell and Developmental Biology, Vanderbilt University, Nashville, 
      TN 37232, USA.
FAU - Singh, Bhuminder
AU  - Singh B
FAU - Higginbotham, James N
AU  - Higginbotham JN
FAU - Franklin, Jeffrey L
AU  - Franklin JL
FAU - Gonzalez, Alfonso
AU  - Gonzalez A
FAU - Folsch, Heike
AU  - Folsch H
FAU - Coffey, Robert J
AU  - Coffey RJ
LA  - eng
GR  - P30 DK058404-07/DK/NIDDK NIH HHS/United States
GR  - P30 DK058404/DK/NIDDK NIH HHS/United States
GR  - P30 HD015052/HD/NICHD NIH HHS/United States
GR  - EY08126/EY/NEI NIH HHS/United States
GR  - P30 CA068485-15/CA/NCI NIH HHS/United States
GR  - P30 EY008126/EY/NEI NIH HHS/United States
GR  - P50 CA095103-09/CA/NCI NIH HHS/United States
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - DK20593/DK/NIDDK NIH HHS/United States
GR  - U24 DK059637/DK/NIDDK NIH HHS/United States
GR  - R01 CA046413-23/CA/NCI NIH HHS/United States
GR  - P60 DK020593/DK/NIDDK NIH HHS/United States
GR  - T32 CA009582/CA/NCI NIH HHS/United States
GR  - P50 CA095103/CA/NCI NIH HHS/United States
GR  - CA095103/CA/NCI NIH HHS/United States
GR  - T32 CA009582-21/CA/NCI NIH HHS/United States
GR  - R01 CA046413/CA/NCI NIH HHS/United States
GR  - P60 DK020593-30/DK/NIDDK NIH HHS/United States
GR  - DK58404/DK/NIDDK NIH HHS/United States
GR  - 2 T32 CA009582/CA/NCI NIH HHS/United States
GR  - DK59637/DK/NIDDK NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - R01 GM070736/GM/NIGMS NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - U24 DK059637-07/DK/NIDDK NIH HHS/United States
GR  - CA046413/CA/NCI NIH HHS/United States
GR  - GM070736/GM/NIGMS NIH HHS/United States
GR  - P30 EY008126-16/EY/NEI NIH HHS/United States
GR  - HD15052/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111013
PL  - England
TA  - Traffic
JT  - Traffic (Copenhagen, Denmark)
JID - 100939340
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Amphiregulin
MH  - Animals
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Cell Polarity/physiology
MH  - Cytoplasm/*metabolism
MH  - Dogs
MH  - EGF Family of Proteins
MH  - Epithelial Cells/metabolism
MH  - ErbB Receptors/metabolism
MH  - Glycoproteins/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - LLC-PK1 Cells
MH  - Leucine/*metabolism
MH  - Membrane Proteins/*metabolism
MH  - Molecular Sequence Data
MH  - Protein Structure, Tertiary/physiology
MH  - Protein Transport
MH  - Receptors, Nerve Growth Factor/metabolism
MH  - Swine
PMC - PMC3886124
MID - NIHMS324508
EDAT- 2011/09/16 06:00
MHDA- 2012/06/05 06:00
PMCR- 2014/01/09
CRDT- 2011/09/16 06:00
PHST- 2011/09/16 06:00 [entrez]
PHST- 2011/09/16 06:00 [pubmed]
PHST- 2012/06/05 06:00 [medline]
PHST- 2014/01/09 00:00 [pmc-release]
AID - 10.1111/j.1600-0854.2011.01282.x [doi]
PST - ppublish
SO  - Traffic. 2011 Dec;12(12):1793-804. doi: 10.1111/j.1600-0854.2011.01282.x. Epub 
      2011 Oct 13.