PMID- 26527400
OWN - NLM
STAT- MEDLINE
DCOM- 20160921
LR  - 20190613
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 128
IP  - 24
DP  - 2015 Dec 15
TI  - AP-2-complex-mediated endocytosis of Drosophila Crumbs regulates polarity by 
      antagonizing Stardust.
PG  - 4538-49
LID - 10.1242/jcs.174573 [doi]
AB  - Maintenance of epithelial polarity depends on the correct localization and levels 
      of polarity determinants. The evolutionarily conserved transmembrane protein 
      Crumbs is crucial for the size and identity of the apical membrane, yet little is 
      known about the molecular mechanisms controlling the amount of Crumbs at the 
      surface. Here, we show that Crumbs levels on the apical membrane depend on a 
      well-balanced state of endocytosis and stabilization. The adaptor protein 2 
      (AP-2) complex binds to a motif in the cytoplasmic tail of Crumbs that overlaps 
      with the binding site of Stardust, a protein known to stabilize Crumbs on the 
      surface. Preventing endocytosis by mutation of AP-2 causes expansion of the 
      Crumbs-positive plasma membrane domain and polarity defects, which can be 
      partially rescued by removing one copy of crumbs. Strikingly, knocking down both 
      AP-2 and Stardust leads to the retention of Crumbs on the membrane. This study 
      provides evidence for a molecular mechanism, based on stabilization and 
      endocytosis, to adjust surface levels of Crumbs, which are essential for 
      maintaining epithelial polarity.
CI  - (c) 2015. Published by The Company of Biologists Ltd.
FAU - Lin, Ya-Huei
AU  - Lin YH
AD  - Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 
      108, Dresden 01307, Germany.
FAU - Currinn, Heather
AU  - Currinn H
AD  - School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham 
      B4 7ET, UK.
FAU - Pocha, Shirin Meher
AU  - Pocha SM
AD  - Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 
      108, Dresden 01307, Germany.
FAU - Rothnie, Alice
AU  - Rothnie A
AD  - School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham 
      B4 7ET, UK.
FAU - Wassmer, Thomas
AU  - Wassmer T
AD  - School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham 
      B4 7ET, UK.
FAU - Knust, Elisabeth
AU  - Knust E
AD  - Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 
      108, Dresden 01307, Germany knust@mpi-cbg.de.
LA  - eng
GR  - BB/K014862/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151102
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Drosophila Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (TfAP-2 protein, Drosophila)
RN  - 0 (Transcription Factor AP-2)
RN  - 0 (crb protein, Drosophila)
RN  - EC 2.7.4.8 (Guanylate Kinases)
RN  - EC 2.7.4.8 (sdt protein, Drosophila)
SB  - IM
MH  - Animals
MH  - Cell Polarity/*physiology
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Drosophila melanogaster
MH  - Endocytosis/*physiology
MH  - Epithelial Cells/cytology/*metabolism
MH  - Guanylate Kinases/genetics/*metabolism
MH  - Membrane Proteins/genetics/*metabolism
MH  - Membrane Transport Proteins/genetics/*metabolism
MH  - Transcription Factor AP-2/genetics/*metabolism
OTO - NOTNLM
OT  - AP-2 complex
OT  - Crumbs
OT  - Endocytosis
OT  - Epithelial polarity
OT  - PDZ-binding
OT  - Stardust
EDAT- 2015/11/04 06:00
MHDA- 2016/09/23 06:00
CRDT- 2015/11/04 06:00
PHST- 2015/05/15 00:00 [received]
PHST- 2015/10/26 00:00 [accepted]
PHST- 2015/11/04 06:00 [entrez]
PHST- 2015/11/04 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
AID - jcs.174573 [pii]
AID - 10.1242/jcs.174573 [doi]
PST - ppublish
SO  - J Cell Sci. 2015 Dec 15;128(24):4538-49. doi: 10.1242/jcs.174573. Epub 2015 Nov 
      2.