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

Abstract

One of the key processes in the inflammatory response is the movement of leukocytes across the endothelium (transendothelial migration, TEM). We have shown that TEM requires a novel endothelial cell compartment, the Lateral Border Recycling Compartment (LBRC), which delivers requisite membrane proteins to surround the migrating leukocyte. In a recent proteomic screen to identify the components of the LBRC we discovered that IQGAP1 is specifically associated with it. Moreover, IQGAP1 is a critical factor in TEM. shRNA mediated knockdown of IQGAP1 expression in endothelial cells significantly impairs their ability to support TEM. In IQGAP1 knockdown cells, the targeted movement of the LBRC to the leukocyte is severely disrupted. This defect is rescued by re‐expression of full length IQGAP1. Using fluorescently tagged IQGAP1 constructs, we can follow IQGAP1 during TEM and have found that it moves with the LBRC to surround the migrating leukocyte. Furthermore, we are performing domain truncations of IQGAP1 to determine which of its many functional interactions are required for TEM. These data suggest that IQGAP1 is an important factor in the regulation of LBRC trafficking during TEM. This research was supported by F32 AI084454 to DPS and R21 HL102519, R01 HL046849, and R37 HL064774 to WAM.