Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension
Abstract
In epithelia, cells are arranged in an orderly pattern with a defined orientation and shape. Cadherin containing apical adherens junctions (AJs) and the associated actomyosin cytoskeleton likely contribute to epithelial cell shape by providing apical tension. The Rho guanosine triphosphatases are well known regulators of cell junction formation, maintenance, and function. Specifically, Rho promotes actomyosin activity and cell contractility; however, what controls and localizes this Rho activity as epithelia remodel is unresolved. Using mosaic clonal analysis in the Drosophila melanogaster pupal eye, we find that Cdc42 is critical for limiting apical cell tension by antagonizing Rho activity at AJs. Cdc42 localizes Par6–atypical protein kinase C (aPKC) to AJs, where this complex limits Rho1 activity and thus actomyosin contractility, independent of its effects on Wiskott-Aldrich syndrome protein and p21-activated kinase. Thus, in addition to its role in the establishment and maintenance of apical–basal polarity in forming epithelia, the Cdc42–Par6–aPKC polarity complex is required to limit Rho activity at AJs and thus modulate apical tension so as to shape the final epithelium.
- Authors:
-
- Washington Univ., St. Louis, MO (United States). Dept. of Medicine; Washington Univ., St. Louis, MO (United States). Dept. of Medicine and Department of Cell Biology and Physiology
- Publication Date:
- Research Org.:
- Washington Univ., St. Louis, MO (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH)
- OSTI Identifier:
- 1625155
- Grant/Contract Number:
- CA85839; GM080673
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Cell Biology
- Additional Journal Information:
- Journal Volume: 187; Journal Issue: 1; Journal ID: ISSN 0021-9525
- Publisher:
- Rockefeller University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Cell Biology
Citation Formats
Warner, Stephen J., and Longmore, Gregory D. Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension. United States: N. p., 2009.
Web. doi:10.1083/jcb.200906047.
Warner, Stephen J., & Longmore, Gregory D. Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension. United States. https://doi.org/10.1083/jcb.200906047
Warner, Stephen J., and Longmore, Gregory D. Mon .
"Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension". United States. https://doi.org/10.1083/jcb.200906047. https://www.osti.gov/servlets/purl/1625155.
@article{osti_1625155,
title = {Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension},
author = {Warner, Stephen J. and Longmore, Gregory D.},
abstractNote = {In epithelia, cells are arranged in an orderly pattern with a defined orientation and shape. Cadherin containing apical adherens junctions (AJs) and the associated actomyosin cytoskeleton likely contribute to epithelial cell shape by providing apical tension. The Rho guanosine triphosphatases are well known regulators of cell junction formation, maintenance, and function. Specifically, Rho promotes actomyosin activity and cell contractility; however, what controls and localizes this Rho activity as epithelia remodel is unresolved. Using mosaic clonal analysis in the Drosophila melanogaster pupal eye, we find that Cdc42 is critical for limiting apical cell tension by antagonizing Rho activity at AJs. Cdc42 localizes Par6–atypical protein kinase C (aPKC) to AJs, where this complex limits Rho1 activity and thus actomyosin contractility, independent of its effects on Wiskott-Aldrich syndrome protein and p21-activated kinase. Thus, in addition to its role in the establishment and maintenance of apical–basal polarity in forming epithelia, the Cdc42–Par6–aPKC polarity complex is required to limit Rho activity at AJs and thus modulate apical tension so as to shape the final epithelium.},
doi = {10.1083/jcb.200906047},
journal = {Journal of Cell Biology},
number = 1,
volume = 187,
place = {United States},
year = {Mon Oct 05 00:00:00 EDT 2009},
month = {Mon Oct 05 00:00:00 EDT 2009}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Surface mechanics mediate pattern formation in the developing retina
journal, October 2004
- Hayashi, Takashi; Carthew, Richard W.
- Nature, Vol. 431, Issue 7009
Cdc42, Par6, and aPKC Regulate Arp2/3-Mediated Endocytosis to Control Local Adherens Junction Stability
journal, November 2008
- Georgiou, Marios; Marinari, Eliana; Burden, Jemima
- Current Biology, Vol. 18, Issue 21
Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors
journal, August 2004
- Bilder, D.
- Genes & Development, Vol. 18, Issue 16
Diaphanous regulates myosin and adherens junctions to control cell contractility and protrusive behavior during morphogenesis
journal, March 2008
- Homem, Catarina C. F.; Peifer, Mark
- Development, Vol. 135, Issue 6
PTEN-Mediated Apical Segregation of Phosphoinositides Controls Epithelial Morphogenesis through Cdc42
journal, January 2007
- Martin-Belmonte, Fernando; Gassama, Ama; Datta, Anirban
- Cell, Vol. 128, Issue 2
Drosophila Cip4 and WASp Define a Branch of the Cdc42-Par6-aPKC Pathway Regulating E-Cadherin Endocytosis
journal, November 2008
- Leibfried, Andrea; Fricke, Robert; Morgan, Matthew J.
- Current Biology, Vol. 18, Issue 21
ROCK and Dia have opposing effects on adherens junctions downstream of Rho
journal, May 2002
- Sahai, Erik; Marshall, Christopher J.
- Nature Cell Biology, Vol. 4, Issue 6
The actin cytoskeleton in cancer cell motility
journal, May 2008
- Olson, Michael F.; Sahai, Erik
- Clinical & Experimental Metastasis, Vol. 26, Issue 4
Par complex in cancer: a regulator of normal cell polarity joins the dark side
journal, November 2008
- Aranda, V.; Nolan, M. E.; Muthuswamy, S. K.
- Oncogene, Vol. 27, Issue 55
Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6–aPKC
journal, September 2007
- Atwood, Scott X.; Chabu, Chiswili; Penkert, Rhiannon R.
- Journal of Cell Science, Vol. 120, Issue 18
The emergence of order in the Drosophila pupal retina
journal, December 1989
- Cagan, Ross L.; Ready, Donald F.
- Developmental Biology, Vol. 136, Issue 2
Mammalian Rho GTPases: new insights into their functions from in vivo studies
journal, September 2008
- Heasman, Sarah J.; Ridley, Anne J.
- Nature Reviews Molecular Cell Biology, Vol. 9, Issue 9
The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells
journal, February 1997
- Ito, K.; Awano, W.; Suzuki, K.
- Development, Vol. 124, Issue 4
Rho and Rac Take Center Stage
text, January 2004
- Krister, Wennerberg,; Keith, Burridge,
- The University of North Carolina at Chapel Hill University Libraries
Cdc42–MRCK and Rho–ROCK signalling cooperate in myosin phosphorylation and cell invasion
journal, February 2005
- Wilkinson, Simon; Paterson, Hugh F.; Marshall, Christopher J.
- Nature Cell Biology, Vol. 7, Issue 3
Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables
journal, November 2003
- Kobielak, Agnieszka; Pasolli, H. Amalia; Fuchs, Elaine
- Nature Cell Biology, Vol. 6, Issue 1
Nonmuscle myosin II moves in new directions
journal, February 2008
- Conti, Mary Anne; Adelstein, Robert S.
- Journal of Cell Science, Vol. 121, Issue 3
The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity
journal, August 2004
- Schwamborn, Jens C.; Püschel, Andreas W.
- Nature Neuroscience, Vol. 7, Issue 9
Claudins in occluding junctions of humans and flies
journal, April 2006
- Furuse, Mikio; Tsukita, Shoichiro
- Trends in Cell Biology, Vol. 16, Issue 4
Regulation of Cell Polarity and Protrusion Formation by Targeting RhoA for Degradation
journal, December 2003
- Wang, H. -R.
- Science, Vol. 302, Issue 5651
Mosaic Analysis with a Repressible Cell Marker for Studies of Gene Function in Neuronal Morphogenesis
journal, March 1999
- Lee, Tzumin; Luo, Liqun
- Neuron, Vol. 22, Issue 3
Combinatorial signaling in the specification of primary pigment cells in the Drosophila eye
journal, March 2007
- Nagaraj, Raghavendra; Banerjee, Utpal
- Development, Vol. 134, Issue 5
Sequential Roles of Cdc42, Par-6, aPKC, and Lgl in the Establishment of Epithelial Polarity during Drosophila Embryogenesis
journal, June 2004
- Hutterer, Andrea; Betschinger, Joerg; Petronczki, Mark
- Developmental Cell, Vol. 6, Issue 6
Compartmentalisation of Rho regulators directs cell invagination during tissue morphogenesis
journal, October 2006
- Simoes, S.; Denholm, B.; Azevedo, D.
- Development, Vol. 133, Issue 21
Cofilin/ADF is required for cell motility during Drosophila ovary development and oogenesis
journal, January 2001
- Chen, Jiong; Godt, Dorothea; Gunsalus, Kris
- Nature Cell Biology, Vol. 3, Issue 2
Distinct functions for Rho1 in maintaining adherens junctions and apical tension in remodeling epithelia
journal, June 2009
- Warner, Stephen J.; Longmore, Gregory D.
- Journal of Cell Biology, Vol. 185, Issue 6
Nonmuscle myosin II moves in new directions
journal, January 2008
- Conti, M. A.; Adelstein, R. S.
- Journal of Cell Science, Vol. 121, Issue 1
Rho-Kinase Phosphorylates PAR-3 and Disrupts PAR Complex Formation
journal, February 2008
- Nakayama, Masanori; Goto, Takaaki M.; Sugimoto, Masayuki
- Developmental Cell, Vol. 14, Issue 2
The PAR-6 Polarity Protein Regulates Dendritic Spine Morphogenesis through p190 RhoGAP and the Rho GTPase
journal, February 2008
- Zhang, Huaye; Macara, Ian G.
- Developmental Cell, Vol. 14, Issue 2
Diaphanous regulates myosin and adherens junctions to control cell contractility and protrusive behavior during morphogenesis
text, January 2008
- C. F., Homem, Catarina; Mark, Peifer,
- The University of North Carolina at Chapel Hill University Libraries
SnapShot: Tight and Adherens Junction Signaling
journal, June 2008
- Harder, Jennifer L.; Margolis, Ben
- Cell, Vol. 133, Issue 6
Chimaerin and Rac regulate cell number, adherens junctions, and ERK MAP kinase signaling in the Drosophila eye
journal, April 2007
- Bruinsma, S. P.; Cagan, R. L.; Baranski, T. J.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 17
Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neuroectoderm through regulation of apical endocytosis
journal, December 2008
- Harris, Kathryn P.; Tepass, Ulrich
- Journal of Cell Biology, Vol. 183, Issue 6
Gene Targeting of Cdc42 and Cdc42GAP Affirms the Critical Involvement of Cdc42 in Filopodia Induction, Directed Migration, and Proliferation in Primary Mouse Embryonic Fibroblasts
journal, November 2006
- Yang, Linda; Wang, Lei; Zheng, Yi
- Molecular Biology of the Cell, Vol. 17, Issue 11
Morphogenetic Cell Movements: Diversity from Modular Mechanical Properties
journal, December 2008
- Montell, D. J.
- Science, Vol. 322, Issue 5907
Preferential Adhesion Mediated by Hibris and Roughest Regulates Morphogenesis and Patterning in the Drosophila Eye
journal, June 2005
- Bao, Sujin; Cagan, Ross
- Developmental Cell, Vol. 8, Issue 6
Control of Actin Reorganization by Slingshot, a Family of Phosphatases that Dephosphorylate ADF/Cofilin
journal, January 2002
- Niwa, Ryusuke; Nagata-Ohashi, Kyoko; Takeichi, Masatoshi
- Cell, Vol. 108, Issue 2
Rho-kinase regulates tissue morphogenesis via non-muscle myosin and LIM-kinase during Drosophiladevelopment
journal, August 2006
- Verdier, Valerie; Chen, Guang-Chao; Settleman, Jeffrey
- BMC Developmental Biology, Vol. 6, Issue 1
The actin cytoskeleton in cancer cell motility
journal, May 2008
- Olson, Michael F.; Sahai, Erik
- Clinical & Experimental Metastasis, Vol. 26, Issue 4
The emergence of order in the Drosophila pupal retina
journal, December 1989
- Cagan, Ross L.; Ready, Donald F.
- Developmental Biology, Vol. 136, Issue 2
Phosphoinositides Specify Polarity during Epithelial Organ Development
journal, January 2007
- Comer, Frank I.; Parent, Carole A.
- Cell, Vol. 128, Issue 2
SnapShot: Tight and Adherens Junction Signaling
journal, June 2008
- Harder, Jennifer L.; Margolis, Ben
- Cell, Vol. 133, Issue 6
Intercellular Junctions: Actin the PARt
journal, November 2008
- Shen, Le; Turner, Jerrold R.
- Current Biology, Vol. 18, Issue 21
Sequential Roles of Cdc42, Par-6, aPKC, and Lgl in the Establishment of Epithelial Polarity during Drosophila Embryogenesis
journal, June 2004
- Hutterer, Andrea; Betschinger, Joerg; Petronczki, Mark
- Developmental Cell, Vol. 6, Issue 6
The PAR-6 Polarity Protein Regulates Dendritic Spine Morphogenesis through p190 RhoGAP and the Rho GTPase
journal, February 2008
- Zhang, Huaye; Macara, Ian G.
- Developmental Cell, Vol. 14, Issue 2
Rho-Kinase Phosphorylates PAR-3 and Disrupts PAR Complex Formation
journal, February 2008
- Nakayama, Masanori; Goto, Takaaki M.; Sugimoto, Masayuki
- Developmental Cell, Vol. 14, Issue 2
Rho and Rac Take Center Stage
journal, January 2004
- Burridge, Keith; Wennerberg, Krister
- Cell, Vol. 116, Issue 2
Cell polarity: the ups and downs of the Par6/aPKC complex
journal, August 2003
- Henrique, D.
- Current Opinion in Genetics & Development, Vol. 13, Issue 4
Surface mechanics mediate pattern formation in the developing retina
journal, October 2004
- Hayashi, Takashi; Carthew, Richard W.
- Nature, Vol. 431, Issue 7009
Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables
journal, November 2003
- Kobielak, Agnieszka; Pasolli, H. Amalia; Fuchs, Elaine
- Nature Cell Biology, Vol. 6, Issue 1
Cdc42–MRCK and Rho–ROCK signalling cooperate in myosin phosphorylation and cell invasion
journal, February 2005
- Wilkinson, Simon; Paterson, Hugh F.; Marshall, Christopher J.
- Nature Cell Biology, Vol. 7, Issue 3
The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity
journal, August 2004
- Schwamborn, Jens C.; Püschel, Andreas W.
- Nature Neuroscience, Vol. 7, Issue 9
Mammalian Rho GTPases: new insights into their functions from in vivo studies
journal, September 2008
- Heasman, Sarah J.; Ridley, Anne J.
- Nature Reviews Molecular Cell Biology, Vol. 9, Issue 9
Par complex in cancer: a regulator of normal cell polarity joins the dark side
journal, November 2008
- Aranda, V.; Nolan, M. E.; Muthuswamy, S. K.
- Oncogene, Vol. 27, Issue 55
Regulating polarity by directing traffic: Cdc42 prevents adherens junctions from Crumblin' aPart
journal, December 2008
- Duncan, Mara C.; Peifer, Mark
- Journal of Cell Biology, Vol. 183, Issue 6
Distinct functions for Rho1 in maintaining adherens junctions and apical tension in remodeling epithelia
journal, June 2009
- Warner, Stephen J.; Longmore, Gregory D.
- Journal of Cell Biology, Vol. 185, Issue 6
Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors
journal, August 2004
- Bilder, D.
- Genes & Development, Vol. 18, Issue 16
Morphogenetic Cell Movements: Diversity from Modular Mechanical Properties
journal, December 2008
- Montell, D. J.
- Science, Vol. 322, Issue 5907
Compartmentalisation of Rho regulators directs cell invagination during tissue morphogenesis
journal, October 2006
- Simoes, S.; Denholm, B.; Azevedo, D.
- Development, Vol. 133, Issue 21
Combinatorial signaling in the specification of primary pigment cells in the Drosophila eye
journal, March 2007
- Nagaraj, Raghavendra; Banerjee, Utpal
- Development, Vol. 134, Issue 5
The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells
journal, February 1997
- Ito, K.; Awano, W.; Suzuki, K.
- Development, Vol. 124, Issue 4
Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6–aPKC
journal, September 2007
- Atwood, Scott X.; Chabu, Chiswili; Penkert, Rhiannon R.
- Journal of Cell Science, Vol. 120, Issue 18
Nonmuscle myosin II moves in new directions
journal, February 2008
- Conti, Mary Anne; Adelstein, Robert S.
- Journal of Cell Science, Vol. 121, Issue 3
Diaphanous regulates myosin and adherens junctions to control cell contractility and protrusive behavior during morphogenesis
text, January 2008
- C. F., Homem, Catarina; Mark, Peifer,
- The University of North Carolina at Chapel Hill University Libraries
Works referencing / citing this record:
Adherens junctions: from molecules to morphogenesis
journal, July 2010
- Harris, Tony J. C.; Tepass, Ulrich
- Nature Reviews Molecular Cell Biology, Vol. 11, Issue 7
Crossroads of integrins and cadherins in epithelia and stroma remodeling
journal, May 2012
- Epifano, Carolina; Perez-Moreno, Mirna
- Cell Adhesion & Migration, Vol. 6, Issue 3
Cellular contractility coordinates cytoskeletal dynamics and cell behaviour during Drosophila abdominal morphogenesis
posted_content, January 2019
- Norris, Anneliese; Bischoff, Marcus; Companys, Pau Pulido
- Semantic Scholar
Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling
journal, March 2011
- Baum, Buzz; Georgiou, Marios
- Journal of Cell Biology, Vol. 192, Issue 6
The interdependence of the Rho GTPases and apicobasal cell polarity
journal, April 2014
- Mack, Natalie Ann; Georgiou, Marios
- Small GTPases, Vol. 5, Issue 2
Adherens Junctions on the Move—Membrane Trafficking of E-Cadherin
journal, January 2017
- Brüser, Lena; Bogdan, Sven
- Cold Spring Harbor Perspectives in Biology, Vol. 9, Issue 3
A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis in fission yeast
journal, November 2019
- Hercyk, Brian S.; Rich-Robinson, Julie; Mitoubsi, Ahmad S.
- Journal of Cell Science, Vol. 132, Issue 23
Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation
journal, June 2011
- Ishiuchi, Takashi; Takeichi, Masatoshi
- Nature Cell Biology, Vol. 13, Issue 7
A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis
posted_content, January 2019
- Hercyk, Brian S.; Rich-Robinson, Julie T.; Mitoubsi, Ahmad S.
- Journal of Cell Science
Mechanosensitive Adaptation of E-Cadherin Turnover across adherens Junctions
journal, June 2015
- de Beco, Simon; Perney, Jean-Baptiste; Coscoy, Sylvie
- PLOS ONE, Vol. 10, Issue 6
Epithelial junctions and Rho family GTPases: the zonular signalosome
journal, October 2014
- Citi, Sandra; Guerrera, Diego; Spadaro, Domenica
- Small GTPases, Vol. 5, Issue 4
Morphogenesis: Multitalented GTPases Seeking New Jobs
journal, November 2009
- Sawyer, Jessica K.; Harris, Nathan J.; Peifer, Mark
- Current Biology, Vol. 19, Issue 21
The Cdc42/Par6/aPKC Polarity Complex Regulates Apoptosis-Induced Compensatory Proliferation in Epithelia
journal, April 2010
- Warner, Stephen J.; Yashiro, Hanako; Longmore, Gregory D.
- Current Biology, Vol. 20, Issue 8
Interplay between the Dividing Cell and Its Neighbors Regulates Adherens Junction Formation during Cytokinesis in Epithelial Tissue
journal, February 2013
- Herszterg, Sophie; Leibfried, Andrea; Bosveld, Floris
- Developmental Cell, Vol. 24, Issue 3
Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling
journal, March 2011
- Baum, Buzz; Georgiou, Marios
- Journal of Cell Biology, Vol. 192, Issue 6
Rap1 and Canoe/afadin are essential for establishment of apical–basal polarity in the Drosophila embryo
journal, April 2013
- Choi, Wangsun; Harris, Nathan J.; Sumigray, Kaelyn D.
- Molecular Biology of the Cell, Vol. 24, Issue 7
Rho1 regulates adherens junction remodeling by promoting recycling endosome formation through activation of myosin II
journal, October 2014
- Yashiro, Hanako; Loza, Andrew J.; Skeath, James B.
- Molecular Biology of the Cell, Vol. 25, Issue 19
A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis
posted_content, January 2019
- Hercyk, Brian S.; Rich-Robinson, Julie T.; Mitoubsi, Ahmad S.
- Journal of Cell Science
Thyroid bud morphogenesis requires CDC42- and SHROOM3-dependent apical constriction
journal, January 2016
- Loebel, David A. F.; Plageman, Timothy F.; Tang, Theresa L.
- Biology Open, Vol. 5, Issue 2
Mechanosensitive Adaptation of E-Cadherin Turnover across adherens Junctions
journal, June 2015
- de Beco, Simon; Perney, Jean-Baptiste; Coscoy, Sylvie
- PLOS ONE, Vol. 10, Issue 6
Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms
journal, July 2016
- Schimizzi, Gregory V.; Maher, Meghan T.; Loza, Andrew J.
- PLOS ONE, Vol. 11, Issue 7
Rab11 Helps Maintain Apical Crumbs and Adherens Junctions in the Drosophila Embryonic Ectoderm
text, January 2009
- Mark, Peifer,; K., Sawyer, Jessica; F., Roeth, Jeremiah
- The University of North Carolina at Chapel Hill University Libraries
Epithelial junctions and Rho family GTPases: the zonular signalosome
journal, October 2014
- Citi, Sandra; Guerrera, Diego; Spadaro, Domenica
- Small GTPases, Vol. 5, Issue 4
The interdependence of the Rho GTPases and apicobasal cell polarity
journal, April 2014
- Mack, Natalie Ann; Georgiou, Marios
- Small GTPases, Vol. 5, Issue 2