TY - JOUR
T1 - Endothelial cells use dynamic actin to facilitate lymphocyte transendothelial migration and maintain the monolayer barrier
AU - Mooren, Olivia L.
AU - Li, Jinmei
AU - Nawas, Julie
AU - Cooper, John A.
N1 - Publisher Copyright:
© 2014 Mooren et al.
PY - 2014/12/15
Y1 - 2014/12/15
N2 - The vascular endothelium is a highly dynamic structure, and the integrity of its barrier function is tightly regulated. Normally impenetrable to cells, the endothelium actively assists lymphocytes to exit the bloodstream during inflammation. The actin cytoskeleton of the endothelial cell (EC) is known to facilitate transmigration, but the cellular and molecular mechanisms are not well understood. Here we report that actin assembly in the EC, induced by Arp2/3 complex under control of WAVE2, is important for several steps in the process of transmigration. To begin transmigration, ECs deploy actin-based membrane protrusions that create a cup-shaped docking structure for the lymphocyte. We found that docking structure formation involves the localization and activation of Arp2/3 complex by WAVE2. The next step in transmigration is creation of a migratory pore, and we found that endothelial WAVE2 is needed for lymphocytes to follow a transcellular route through an EC. Later, ECs use actin- based protrusions to close the gap behind the lymphocyte, which we discovered is also driven by WAVE2. Finally, we found that ECs in resting endothelial monolayers use lamellipo? dial protrusions dependent on WAVE2 to form and maintain contacts and junctions between cells.
AB - The vascular endothelium is a highly dynamic structure, and the integrity of its barrier function is tightly regulated. Normally impenetrable to cells, the endothelium actively assists lymphocytes to exit the bloodstream during inflammation. The actin cytoskeleton of the endothelial cell (EC) is known to facilitate transmigration, but the cellular and molecular mechanisms are not well understood. Here we report that actin assembly in the EC, induced by Arp2/3 complex under control of WAVE2, is important for several steps in the process of transmigration. To begin transmigration, ECs deploy actin-based membrane protrusions that create a cup-shaped docking structure for the lymphocyte. We found that docking structure formation involves the localization and activation of Arp2/3 complex by WAVE2. The next step in transmigration is creation of a migratory pore, and we found that endothelial WAVE2 is needed for lymphocytes to follow a transcellular route through an EC. Later, ECs use actin- based protrusions to close the gap behind the lymphocyte, which we discovered is also driven by WAVE2. Finally, we found that ECs in resting endothelial monolayers use lamellipo? dial protrusions dependent on WAVE2 to form and maintain contacts and junctions between cells.
UR - http://www.scopus.com/inward/record.url?scp=84918539557&partnerID=8YFLogxK
U2 - 10.1091/mbc.E14-05-0976
DO - 10.1091/mbc.E14-05-0976
M3 - Article
C2 - 25355948
AN - SCOPUS:84918539557
SN - 1059-1524
VL - 25
SP - 4115
EP - 4129
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 25
ER -