Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1

Xuan Liang, Srikanth Budnar, Shafali Gupta, Suzie Verma, Siew Ping Han, Michelle M. Hill, Roger J. Daly, Robert G. Parton, Nicholas A. Hamilton, Guillermo A. Gomez, Alpha S. Yap

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Contractile adherens junctions support cell-cell adhesion, epithelial integrity, and morphogenesis. Much effort has been devoted to understanding how contractility is established; however, less is known about whether contractility can be actively downregulated at junctions nor what function this might serve. We now identify such an inhibitory pathway that is mediated by the cytoskeletal scaffold, cortactin. Mutations of cortactin that prevent its tyrosine phosphorylation downregulate RhoA signaling and compromise the ability of epithelial cells to generate a contractile zonula adherens. This is mediated by the RhoA antagonist, SRGAP1. We further demonstrate that this mechanism is co-opted by hepatocyte growth factor to promote junctional relaxation and motility in epithelial collectives. Together, our findings identify a novel function of cortactin as a regulator of RhoA signaling that can be utilized by morphogenetic regulators for the active downregulation of junctional contractility.

Original languageEnglish
Article number790
Number of pages15
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • adherens junctions
  • cadherins
  • collective cell migration

Cite this

Liang, Xuan ; Budnar, Srikanth ; Gupta, Shafali ; Verma, Suzie ; Han, Siew Ping ; Hill, Michelle M. ; Daly, Roger J. ; Parton, Robert G. ; Hamilton, Nicholas A. ; Gomez, Guillermo A. ; Yap, Alpha S. / Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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abstract = "Contractile adherens junctions support cell-cell adhesion, epithelial integrity, and morphogenesis. Much effort has been devoted to understanding how contractility is established; however, less is known about whether contractility can be actively downregulated at junctions nor what function this might serve. We now identify such an inhibitory pathway that is mediated by the cytoskeletal scaffold, cortactin. Mutations of cortactin that prevent its tyrosine phosphorylation downregulate RhoA signaling and compromise the ability of epithelial cells to generate a contractile zonula adherens. This is mediated by the RhoA antagonist, SRGAP1. We further demonstrate that this mechanism is co-opted by hepatocyte growth factor to promote junctional relaxation and motility in epithelial collectives. Together, our findings identify a novel function of cortactin as a regulator of RhoA signaling that can be utilized by morphogenetic regulators for the active downregulation of junctional contractility.",
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Liang, X, Budnar, S, Gupta, S, Verma, S, Han, SP, Hill, MM, Daly, RJ, Parton, RG, Hamilton, NA, Gomez, GA & Yap, AS 2017, 'Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1', Nature Communications, vol. 8, no. 1, 790. https://doi.org/10.1038/s41467-017-00797-w

Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1. / Liang, Xuan; Budnar, Srikanth; Gupta, Shafali; Verma, Suzie; Han, Siew Ping; Hill, Michelle M.; Daly, Roger J.; Parton, Robert G.; Hamilton, Nicholas A.; Gomez, Guillermo A.; Yap, Alpha S.

In: Nature Communications, Vol. 8, No. 1, 790, 01.12.2017.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Han, Siew Ping

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AU - Parton, Robert G.

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