Mechanisms controlling human endothelial lumen formation and tube assembly in three-dimensional extracellular matrices

2007 ◽  
Vol 81 (4) ◽  
pp. 270-285 ◽  
Author(s):  
George E. Davis ◽  
Wonshill Koh ◽  
Amber N. Stratman
2012 ◽  
Vol 195 (1-2) ◽  
pp. 122-143 ◽  
Author(s):  
Anastasia Sacharidou ◽  
Amber N. Stratman ◽  
George E. Davis

2002 ◽  
Vol 115 (6) ◽  
pp. 1123-1136 ◽  
Author(s):  
Kayla J. Bayless ◽  
George E. Davis

Here we show a requirement for the Cdc42 and Rac1 GTPases in endothelial cell (EC) morphogenesis in three-dimensional extracellular matrices. Cdc42 and Rac1 specifically regulate EC intracellular vacuole and lumen formation in both collagen and fibrin matrices. Clostridium difficile toxin B(which blocks all three Rho GTPases) completely inhibited the ability of ECs to form both vacuoles and lumens, whereas C3 transferase, a selective inhibitor of Rho, did not. Expression of either dominant-negative (N17) or constitutively active (V12) Cdc42 using recombinant adenoviruses dramatically inhibited EC vacuole and lumen formation in both collagen and fibrin matrices. Both vacuole and lumen formation initiated in ECs expressing dominant-negative(N17) Rac1 but later collapsed, indicating a role for Rac1 during later stages of vessel development. Analysis of cultures using confocal microscopy revealed green fluorescent protein-V12Rac1, -Rac1 wild-type and -Cdc42 wild-type chimeric proteins targeted to intracellular vacuole membranes during the lumen formation process. Also, expression of the verprolin-cofilin-acidic domain of N-WASP, a downstream Cdc42 effector, in ECs completely interfered with vacuole and lumen formation. These results collectively reveal a novel role for Cdc42 and Rac1 in the process of EC vacuole and lumen formation in three-dimensional extracellular matrices.


1999 ◽  
Vol 155 (3) ◽  
pp. 887-895 ◽  
Author(s):  
Suya Yang ◽  
Jennifer Graham ◽  
Jeanne W. Kahn ◽  
Eric A. Schwartz ◽  
Mary E. Gerritsen

2008 ◽  
Vol 13 (2) ◽  
pp. A28-A48
Author(s):  
N.R. Washburn ◽  
M.D. Weir ◽  
K.M. Yamada

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