Actin can reorganize into podosomes in aortic endothelial cells, a process controlled by Cdc42 and RhoA

Mol Cell Biol. 2003 Oct;23(19):6809-22. doi: 10.1128/MCB.23.19.6809-6822.2003.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Actins / physiology*
  • Animals
  • Aorta / cytology*
  • Bacterial Toxins / pharmacology
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Cytoskeletal Proteins
  • Cytoskeleton / metabolism
  • Cytotoxins / pharmacology
  • Down-Regulation
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Endothelium, Vascular / transplantation
  • Escherichia coli Proteins*
  • Glutathione Transferase / pharmacology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mutation
  • Nerve Growth Factors
  • Proteins / metabolism
  • Pseudopodia / drug effects
  • Pseudopodia / physiology*
  • Recombinant Proteins / metabolism
  • Swine
  • Trans-Activators / metabolism
  • cdc42 GTP-Binding Protein / drug effects
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism*
  • rhoA GTP-Binding Protein / drug effects
  • rhoA GTP-Binding Protein / metabolism*


  • Actins
  • Bacterial Toxins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Cytotoxins
  • Escherichia coli Proteins
  • Intracellular Signaling Peptides and Proteins
  • MANF protein, human
  • Nerve Growth Factors
  • Proteins
  • Recombinant Proteins
  • Trans-Activators
  • WIPF1 protein, human
  • cytotoxic necrotizing factor type 1
  • Glutathione Transferase
  • cdc42 GTP-Binding Protein
  • rhoA GTP-Binding Protein