PMID- 29731302
OWN - NLM
STAT- MEDLINE
DCOM- 20191015
LR  - 20220129
IS  - 1879-0445 (Electronic)
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 28
IP  - 10
DP  - 2018 May 21
TI  - Quantitative Control of GPCR Organization and Signaling by Endocytosis in 
      Epithelial Morphogenesis.
PG  - 1570-1584.e6
LID - S0960-9822(18)30426-3 [pii]
LID - 10.1016/j.cub.2018.03.068 [doi]
AB  - Tissue morphogenesis arises from controlled cell deformations in response to 
      cellular contractility. During Drosophila gastrulation, apical activation of the 
      actomyosin networks drives apical constriction in the invaginating mesoderm and 
      cell-cell intercalation in the extending ectoderm. Myosin II (MyoII) is activated 
      by cell-surface G protein-coupled receptors (GPCRs), such as Smog and Mist, that 
      activate G proteins, the small GTPase Rho1, and the kinase Rok. Quantitative 
      control over GPCR and Rho1 activation underlies differences in deformation of 
      mesoderm and ectoderm cells. We show that GPCR Smog activity is concentrated on 
      two different apical plasma membrane compartments, i.e., the surface and plasma 
      membrane invaginations. Using fluorescence correlation spectroscopy, we probe the 
      surface of the plasma membrane, and we show that Smog homo-clusters in response 
      to its activating ligand Fog. Endocytosis of Smog is regulated by the kinase 
      Gprk2 and beta-arrestin-2 that clears active Smog from the plasma membrane. When Fog 
      concentration is high or endocytosis is low, Smog rearranges in homo-clusters and 
      accumulates in plasma membrane invaginations that are hubs for Rho1 activation. 
      Lastly, we find higher Smog homo-cluster concentration and numerous apical plasma 
      membrane invaginations in the mesoderm compared to the ectoderm, indicative of 
      reduced endocytosis. We identify that dynamic partitioning of active Smog at the 
      surface of the plasma membrane or plasma membrane invaginations has a direct 
      impact on Rho1 signaling. Plasma membrane invaginations accumulate high 
      Rho1-guanosine triphosphate (GTP) suggesting they form signaling centers. Thus, 
      Fog concentration and Smog endocytosis form coupled regulatory processes that 
      regulate differential Rho1 and MyoII activation in the Drosophila embryo.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Jha, Ankita
AU  - Jha A
AD  - Aix Marseille Universite, CNRS, IBDM - UMR7288, Turing Centre for Living Systems, 
      Marseille, France.
FAU - van Zanten, Thomas S
AU  - van Zanten TS
AD  - National Centre for Biological Sciences, TIFR, Bangalore 560065, India.
FAU - Philippe, Jean-Marc
AU  - Philippe JM
AD  - Aix Marseille Universite, CNRS, IBDM - UMR7288, Turing Centre for Living Systems, 
      Marseille, France.
FAU - Mayor, Satyajit
AU  - Mayor S
AD  - National Centre for Biological Sciences, TIFR, Bangalore 560065, India.
FAU - Lecuit, Thomas
AU  - Lecuit T
AD  - Aix Marseille Universite, CNRS, IBDM - UMR7288, Turing Centre for Living Systems, 
      Marseille, France; College de France, 11 Place Marcelin Berthelot, Paris, France. 
      Electronic address: thomas.lecuit@univ-amu.fr.
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - IA/M/15/1/502018/WTDBT_/DBT-Wellcome Trust India Alliance/India
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180503
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
SB  - IM
MH  - Animals
MH  - Drosophila melanogaster/genetics/*physiology
MH  - *Endocytosis
MH  - Epithelium/growth & development
MH  - *Morphogenesis
MH  - Signal Transduction
PMC - PMC6934411
MID - EMS85318
OTO - NOTNLM
OT  - G protein-coupled receptor
OT  - G protein-coupled receptor kinase
OT  - acto-myosin contractility
OT  - endocytosis
OT  - epithelial morphogenesis
OT  - fluorescence correlation spectroscopy
OT  - gastrulation
OT  - beta-arrestin
COIS- Declaration of Interests The authors declare no competing interests.
EDAT- 2018/05/08 06:00
MHDA- 2019/10/16 06:00
PMCR- 2019/12/27
CRDT- 2018/05/08 06:00
PHST- 2017/10/05 00:00 [received]
PHST- 2018/01/16 00:00 [revised]
PHST- 2018/03/29 00:00 [accepted]
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2019/10/16 06:00 [medline]
PHST- 2018/05/08 06:00 [entrez]
PHST- 2019/12/27 00:00 [pmc-release]
AID - S0960-9822(18)30426-3 [pii]
AID - 10.1016/j.cub.2018.03.068 [doi]
PST - ppublish
SO  - Curr Biol. 2018 May 21;28(10):1570-1584.e6. doi: 10.1016/j.cub.2018.03.068. Epub 
      2018 May 3.