title: Regulatory signals for endothelial podosome formation.
abstract: Podosomes are punctate actin-rich adhesion structures which spontaneously form in cells of the myelomonocytic lineage. Their formation is dependent on Src and RhoGTPases. Recently, podosomes have also been described in vascular cells. These podosomes differ from the former by the fact that they are inducible. In endothelial cells, such a signal can be provided by either constitutively active Cdc42, the PKC activator PMA or TGFbeta, depending on the model. Consequently, other regulatory pathways have been reported to contribute to podosome formation. To get more insight into the mechanisms by which podosomes form in endothelial cells, we have explored the respective contribution of signal transducers such as Cdc42-related GTPases, Smads and PKCs in three endothelial cell models. Results presented demonstrate that, in addition to Cdc42, TC10 and TCL GTPases can also promote podosome formation in endothelial cells. We also show that PKCalpha can be either necessary or entirely dispensable, depending on the cell model. In contrast, PKCdelta is essential for podosome formation in endothelial cells but not smooth muscle cells. Finally, although podosomes vary very little in their molecular composition, the signalling pathways involved in their assembly appear very diverse.
authors.affiliation: Institut Européen de Chimie-Biologie, Université Bordeaux 1, Pessac, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Billottet
authors.forename: Patricia
authors.initials: P
authors.lastname: Rottiers
authors.forename: Florence
authors.initials: F
authors.lastname: Tatin
authors.forename: Christine
authors.initials: C
authors.lastname: Varon
authors.forename: Edith
authors.initials: E
authors.lastname: Reuzeau
authors.forename: Jean-Léon
authors.initials: JL
authors.lastname: Maître
authors.forename: Frédéric
authors.initials: F
authors.lastname: Saltel
authors.forename: Violaine
authors.initials: V
authors.lastname: Moreau
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Génot
mesh_terms: D008841:Actin Cytoskeleton / Q000201:enzymology* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D013552:Swine; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D051785:Smad Proteins; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D020764:cdc42 GTP-Binding Protein