Endothelial cell IQGAP1 is an important regulator of the transendothelial migration of leukocytes

Abstract

The movement of leukocytes across the endothelium (transendothelial migration, TEM) into tissue is a complex process that is critical for both beneficial and deleterious inflammation. Our lab recently identified a novel endothelial cell compartment, (the Lateral Border Recycling Compartment, LBRC) that delivers critical membrane proteins to surround the migrating leukocyte and is required for TEM. Despite its importance in inflammation, the protein composition of the LBRC is largely unknown. Using biochemistry and subcellular fractionation we recently identified IQGAP1 as a protein associated with the LBRC. Our data indicate that IQGAP1 is required for TEM and is likely involved with regulating LBRC function during TEM. siRNA mediated knockdown of IQGAP1 expression in endothelial cells significantly impairs their ability to support TEM without altering the structure or size of the LBRC. Furthermore, IQGAP1 appears to be recruited to the site of transmigration along with the LBRC. These data suggest that IQGAP1 is involved in the regulation of LBRC trafficking during TEM. This research was supported by F32 AI084454 to DPS and R01 HL046849, R37 HL064774, and R21 HL102519 to WAM.