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Molecular and Cellular Biology, July 2009, p. 3915-3928, Vol. 29, No. 14
0270-7306/09/$08.00+0     doi:10.1128/MCB.01199-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

NADPH Oxidase 1 Controls the Persistence of Directed Cell Migration by a Rho-Dependent Switch of {alpha}2/{alpha}3 Integrins{triangledown} ,{dagger}

Amine Sadok,1 Anne Pierres,2 Laetitia Dahan,1 Charles Prévôt,1 Maxime Lehmann,1 and Hervé Kovacic1*

INSERM UMR 911, CRO2, Faculté de Pharmacie, Aix-Marseille Université, Marseille, France,1 INSERM UMR 600-CNRS UMR 6212, Adhésion cellulaire et inflammation, Aix-Marseille Université, Marseille, France2

Received 30 July 2008/ Returned for modification 1 October 2008/ Accepted 12 May 2009

NADPH oxidase 1 (Nox1) is expressed mainly in colon epithelial cells and produces superoxide ions as a primary function. We showed that Nox1 knockdown inhibits directional persistence of migration on collagen I. This paper dissects the mechanism by which Nox1 affects the direction of colonic epithelial cell migration in a two-dimensional model. Transient activation of Nox1 during cell spreading on collagen 1 temporarily inactivated RhoA and led to efficient exportation of {alpha}2β1 integrin to the cell surface, which supported persistent directed migration. Nox1 knockdown led to a loss of directional migration which takes place through a RhoA-dependent {alpha}2/{alpha}3 integrin switch. Transient RhoA overactivation upon Nox1 inhibition led to transient cytoskeletal reorganization and increased cell-matrix contact associated with a stable increase in {alpha}3 integrin cell surface expression. Blocking of {alpha}3 integrin completely reversed the loss of directional persistence of migration. In this model, Nox1 would represent a switch between random and directional migration through RhoA-dependent integrin cell surface expression modulation.

* Corresponding author. Mailing address: INSERM UMR 911, Centre de Recherche en Oncologie biologique et en Oncopharmacologie, Faculté de Pharmacie, Aix-Marseille Université, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France. Phone: (33) 491 835 627. Fax: (33) 491 835 506. E-mail: hkovacic{at}univmed.fr

{triangledown} Published ahead of print on 18 May 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, July 2009, p. 3915-3928, Vol. 29, No. 14
0270-7306/09/$08.00+0     doi:10.1128/MCB.01199-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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