Actin can reorganize into podosomes in aortic endothelial cells, a process controlled by Cdc42 and RhoA.
TLDR
Punctate filamentous actin structures appeared along the ventral plasma membrane of endothelial cells and were identified as the core of podosomes by the distinctive vinculin ring around the F-actin.Abstract:
Members of the Rho GTPase family play a central role in the orchestration of cytoskeletal rearrangements, which are of prime importance in endothelial cell physiology. To explore their role in this specialized cell type, we used the bacterial toxin cytotoxic necrotizing factor 1 (CNF1) as a Rho GTPase activator. Punctate filamentous actin structures appeared along the ventral plasma membrane of endothelial cells and were identified as the core of podosomes by the distinctive vinculin ring around the F-actin. Rho, Rac, and Cdc42 were all identified as targets of CNF1, but only a constitutively active mutant of Cdc42 could substitute for CNF1 in podosome induction. Accordingly, organization of F-actin in these structures was highly dependent on the main Cdc42 cytoskeletal effector N-Wiskott-Aldrich syndrome protein. Other components of the actin machinery such as Arp2/3 and for the first time WIP also colocalized at these sites. Like CNF1 treatment, sustained Cdc42 activity induced a time-dependent F-actin-vinculin reorganization, prevented cytokinesis, and downregulated Rho activity. Finally, podosomes were also detected on endothelial cells explanted from patients undergoing cardiac surgery. These data provide the first description of podosomes in endothelial cells. The identification of such specialized structures opens up a new field of investigation in terms of endothelium pathophysiology.read more
Citations
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The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function.
TL;DR: Understanding of the regulatory and functional aspects of podosome and invadopodium biology and their role in human disease is improved.
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Cell migration in tumors
TL;DR: These results, combined with new findings from in vitro studies, have led to new insights into the molecular mechanisms of cell protrusive activity and chemotactic migration during invasion and metastasis.
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The matrix corroded: podosomes and invadopodia in extracellular matrix degradation.
TL;DR: This review highlights important new developments in the field, discusses the common and divergent features of podosomes and invadopodia and summarizes current knowledge about matrix-degrading proteinases at these structures.
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Molecular mechanisms of invadopodium formation the role of the N-WASP–Arp2/3 complex pathway and cofilin
Hideki Yamaguchi,Mike Lorenz,Stephan J. Kempiak,Corina Sarmiento,Salvatore J. Coniglio,Marc Symons,Jeffrey E. Segall,Robert J. Eddy,Hiroaki Miki,Tadaomi Takenawa,John S. Condeelis +10 more
TL;DR: Results indicate that EGF receptor signaling regulatesInvadopodium formation through the N-WASP–Arp2/3 pathway and cofilin is necessary for the stabilization and maturation of invadopodia.
Journal ArticleDOI
Assembly and biological role of podosomes and invadopodia.
TL;DR: Recent work has re-discovered prominent actin-based cellular structures, termed invadopodia and podosomes, as unique structural and functional modules through which major invasive mechanisms are regulated.
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