PMID- 21666802
OWN - NLM
STAT- MEDLINE
DCOM- 20111216
LR  - 20220129
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 9
IP  - 6
DP  - 2011 Jun
TI  - Zyxin links fat signaling to the hippo pathway.
PG  - e1000624
LID - 10.1371/journal.pbio.1000624 [doi]
LID - e1000624
AB  - The Hippo signaling pathway has a conserved role in growth control and is of 
      fundamental importance during both normal development and oncogenesis. Despite 
      rapid progress in recent years, key steps in the pathway remain poorly 
      understood, in part due to the incomplete identification of components. Through a 
      genetic screen, we identified the Drosophila Zyxin family gene, Zyx102 (Zyx), as 
      a component of the Hippo pathway. Zyx positively regulates the Hippo pathway 
      transcriptional co-activator Yorkie, as its loss reduces Yorkie activity and 
      organ growth. Through epistasis tests, we position the requirement for Zyx within 
      the Fat branch of Hippo signaling, downstream of Fat and Dco, and upstream of the 
      Yorkie kinase Warts, and we find that Zyx is required for the influence of Fat on 
      Warts protein levels. Zyx localizes to the sub-apical membrane, with distinctive 
      peaks of accumulation at intercellular vertices. This partially overlaps the 
      membrane localization of the myosin Dachs, which has similar effects on Fat-Hippo 
      signaling. Co-immunoprecipitation experiments show that Zyx can bind to Dachs and 
      that Dachs stimulates binding of Zyx to Warts. We also extend characterization of 
      the Ajuba LIM protein Jub and determine that although Jub and Zyx share 
      C-terminal LIM domains, they regulate Hippo signaling in distinct ways. Our 
      results identify a role for Zyx in the Hippo pathway and suggest a mechanism for 
      the role of Dachs: because Fat regulates the localization of Dachs to the 
      membrane, where it can overlap with Zyx, we propose that the regulated 
      localization of Dachs influences downstream signaling by modulating Zyx-Warts 
      binding. Mammalian Zyxin proteins have been implicated in linking effects of 
      mechanical strain to cell behavior. Our identification of Zyx as a regulator of 
      Hippo signaling thus also raises the possibility that mechanical strain could be 
      linked to the regulation of gene expression and growth through Hippo signaling.
FAU - Rauskolb, Cordelia
AU  - Rauskolb C
AD  - Howard Hughes Medical Institute, Waksman Institute, and Department of Molecular 
      Biology and Biochemistry, Rutgers, The State University of New Jersey, 
      Piscataway, New Jersey, United States of America.
FAU - Pan, Guohui
AU  - Pan G
FAU - Reddy, B V V G
AU  - Reddy BV
FAU - Oh, Hyangyee
AU  - Oh H
FAU - Irvine, Kenneth D
AU  - Irvine KD
LA  - eng
GR  - HHMI_/Howard Hughes Medical Institute/United States
GR  - R01 GM078620/GM/NIGMS NIH HHS/United States
GR  - GM078620/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110607
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Zyx protein, Drosophila)
RN  - 0 (Zyxin)
RN  - 0 (ft protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (hpo protein, Drosophila)
SB  - IM
MH  - Animals
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Membrane/metabolism
MH  - Drosophila Proteins/*metabolism
MH  - Drosophila melanogaster/cytology/*metabolism
MH  - Epistasis, Genetic
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Models, Biological
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Protein Transport
MH  - *Signal Transduction
MH  - Wings, Animal/cytology/growth & development/metabolism
MH  - Zyxin/*metabolism
PMC - PMC3110180
COIS- The authors have declared that no competing interests exist.
EDAT- 2011/06/15 06:00
MHDA- 2011/12/17 06:00
PMCR- 2011/06/07
CRDT- 2011/06/14 06:00
PHST- 2010/09/15 00:00 [received]
PHST- 2011/04/27 00:00 [accepted]
PHST- 2011/06/14 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2011/12/17 06:00 [medline]
PHST- 2011/06/07 00:00 [pmc-release]
AID - 10-PLBI-RA-9478R3 [pii]
AID - 10.1371/journal.pbio.1000624 [doi]
PST - ppublish
SO  - PLoS Biol. 2011 Jun;9(6):e1000624. doi: 10.1371/journal.pbio.1000624. Epub 2011 
      Jun 7.