The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts

Abstract Levels of active Rac1 at epithelial junctions are partially modulated via interaction with Ajuba, an actin binding and scaffolding protein. Here we demonstrate that Ajuba interacts with the Cdc42 GTPase activating protein CdGAP, a GAP for Rac1 and Cdc42, at cell-cell contacts. CdGAP recruit...

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Autores principales:	J. J. McCormack, S. Bruche, A. B. D. Ouadda, H. Ishii, H. Lu, A. Garcia-Cattaneo, C. Chávez-Olórtegui, N. Lamarche-Vane, V. M. M. Braga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/968899e3245c4560ba7c0878d963ee7d
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spelling	oai:doaj.org-article:968899e3245c4560ba7c0878d963ee7d2021-12-02T11:53:13ZThe scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts10.1038/s41598-017-09024-42045-2322https://doaj.org/article/968899e3245c4560ba7c0878d963ee7d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09024-4https://doaj.org/toc/2045-2322Abstract Levels of active Rac1 at epithelial junctions are partially modulated via interaction with Ajuba, an actin binding and scaffolding protein. Here we demonstrate that Ajuba interacts with the Cdc42 GTPase activating protein CdGAP, a GAP for Rac1 and Cdc42, at cell-cell contacts. CdGAP recruitment to junctions does not require Ajuba; rather Ajuba seems to control CdGAP residence at sites of cell-cell adhesion. CdGAP expression potently perturbs junctions and Ajuba binding inhibits CdGAP activity. Ajuba interacts with Rac1 and CdGAP via distinct domains and can potentially bring them in close proximity at junctions to facilitate activity regulation. Functionally, CdGAP-Ajuba interaction maintains junctional integrity in homeostasis and diseases: (i) gain-of-function CdGAP mutants found in Adams-Oliver Syndrome patients strongly destabilize cell-cell contacts and (ii) CdGAP mRNA levels are inversely correlated with E-cadherin protein expression in different cancers. We present conceptual insights on how Ajuba can integrate CdGAP binding and inactivation with the spatio-temporal regulation of Rac1 activity at junctions. Ajuba provides a novel mechanism due to its ability to bind to CdGAP and Rac1 via distinct domains and influence the activation status of both proteins. This functional interplay may contribute towards conserving the epithelial tissue architecture at steady-state and in different pathologies.J. J. McCormackS. BrucheA. B. D. OuaddaH. IshiiH. LuA. Garcia-CattaneoC. Chávez-OlórteguiN. Lamarche-VaneV. M. M. BragaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q J. J. McCormack S. Bruche A. B. D. Ouadda H. Ishii H. Lu A. Garcia-Cattaneo C. Chávez-Olórtegui N. Lamarche-Vane V. M. M. Braga The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts
description	Abstract Levels of active Rac1 at epithelial junctions are partially modulated via interaction with Ajuba, an actin binding and scaffolding protein. Here we demonstrate that Ajuba interacts with the Cdc42 GTPase activating protein CdGAP, a GAP for Rac1 and Cdc42, at cell-cell contacts. CdGAP recruitment to junctions does not require Ajuba; rather Ajuba seems to control CdGAP residence at sites of cell-cell adhesion. CdGAP expression potently perturbs junctions and Ajuba binding inhibits CdGAP activity. Ajuba interacts with Rac1 and CdGAP via distinct domains and can potentially bring them in close proximity at junctions to facilitate activity regulation. Functionally, CdGAP-Ajuba interaction maintains junctional integrity in homeostasis and diseases: (i) gain-of-function CdGAP mutants found in Adams-Oliver Syndrome patients strongly destabilize cell-cell contacts and (ii) CdGAP mRNA levels are inversely correlated with E-cadherin protein expression in different cancers. We present conceptual insights on how Ajuba can integrate CdGAP binding and inactivation with the spatio-temporal regulation of Rac1 activity at junctions. Ajuba provides a novel mechanism due to its ability to bind to CdGAP and Rac1 via distinct domains and influence the activation status of both proteins. This functional interplay may contribute towards conserving the epithelial tissue architecture at steady-state and in different pathologies.
format	article
author	J. J. McCormack S. Bruche A. B. D. Ouadda H. Ishii H. Lu A. Garcia-Cattaneo C. Chávez-Olórtegui N. Lamarche-Vane V. M. M. Braga
author_facet	J. J. McCormack S. Bruche A. B. D. Ouadda H. Ishii H. Lu A. Garcia-Cattaneo C. Chávez-Olórtegui N. Lamarche-Vane V. M. M. Braga
author_sort	J. J. McCormack
title	The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts
title_short	The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts
title_full	The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts
title_fullStr	The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts
title_full_unstemmed	The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts
title_sort	scaffold protein ajuba suppresses cdgap activity in epithelia to maintain stable cell-cell contacts
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/968899e3245c4560ba7c0878d963ee7d
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The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts

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