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Molecular and Cellular Biology, May 2006, p. 3582-3594, Vol. 26, No. 9
0270-7306/06/$08.00+0 doi:10.1128/MCB.26.9.3582-3594.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Transforming Growth Factor ß Induces Rosettes of Podosomes in Primary Aortic Endothelial Cells
Christine Varon,1,2
Florence Tatin,1,2
Violaine Moreau,1,2
Ellen Van Obberghen-Schilling,3
Samantha Fernandez-Sauze,3
Edith Reuzeau,1,2
Ijsbrand Kramer,1,2 and
Elisabeth Génot1,2*
INSERM Unité 441, University Victor Segalen Bordeaux 2, Bordeaux, France,1
European Institute of Chemistry and Biology, University of Bordeaux I, Talence, France,2
Institute of Signalling, Developmental Biology and Cancer Research, CNRS UMR6543, Centre A, Lacassagne, Nice, France3
Received 11 October 2005/
Returned for modification 28 November 2005/
Accepted 14 February 2006
Cytoskeletal rearrangements are central to endothelial cell physiology and are controlled by soluble factors, matrix proteins, cell-cell interactions, and mechanical forces. We previously reported that aortic endothelial cells can rearrange their cytoskeletons into complex actin-based structures called podosomes when a constitutively active mutant of Cdc42 is expressed. We now report that transforming growth factor beta (TGF-ß) promotes podosome formation in primary aortic endothelial cells. TGF-ß-induced podosomes assembled together into large ring- or crescent-shaped structures. Their formation was dependent on protein synthesis and required functional Src, phosphatidylinositide 3-kinase, Cdc42, RhoA, and Smad signaling. MT1-MMP and metalloprotease 9 (MMP9), both upregulated by TGF-ß, were detected at sites of podosome formation, and MT1-MMP was found to be involved in the local degradation of extracellular matrix proteins beneath the podosomes and required for the invasion of collagen gels by endothelial cells. We propose that TGF-ß plays an important role in endothelial cell physiology by inducing the formation of podosomal structures endowed with metalloprotease activity that may contribute to arterial remodeling.
* Corresponding author. Mailing address: European Institute of Chemistry and Biology, 2 rue Robert Escarpit, 33600, Pessac, France. Phone: 33 (0) 5 40 00 30 56. Fax: 33 (0) 5 40 00 87 26. E-mail:
e.genot{at}iecb.u-bordeaux.fr.
Supplemental material for this article may be found at http://mcb.asm.org/.
Molecular and Cellular Biology, May 2006, p. 3582-3594, Vol. 26, No. 9
0270-7306/06/$08.00+0 doi:10.1128/MCB.26.9.3582-3594.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
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