Regulatory signals for endothelial podosome formation

Podosomes are punctate actin-rich adhesion structures Which spontaneously form in cells of the myelomonocytic lineage. Their formation is dependent oil 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 he provided by either constitutively active Cdc42, the PKC activator PMA or TGF beta, depending oil 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, TOO and TCL GTPases can also promote podosome formation in endothelial cells. We also show that PKC alpha. can be either necessary or entirely dispensable, depending oil the cell model. In contrast, PKC delta 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. (C) 2008 Elsevier GmbH. All rights reserved.