Endothelial IQGAP1 regulates leukocyte transmigration by directing the LBRC to the site of diapedesis

The Journal of Experimental Medicine
David P SullivanWilliam A Muller

Abstract

Transendothelial migration (TEM) of leukocytes across the endothelium is critical for inflammation. In the endothelium, TEM requires the coordination of membrane movements and cytoskeletal interactions, including, prominently, recruitment of the lateral border recycling compartment (LBRC). The scaffold protein IQGAP1 was recently identified in a screen for LBRC-interacting proteins. Knockdown of endothelial IQGAP1 disrupted the directed movement of the LBRC and substantially reduced leukocyte TEM. Expression of truncated IQGAP1 constructs demonstrated that the calponin homology domain is required for IQGAP1 localization to endothelial borders and that the IQ domain, on the same IQGAP1 polypeptide, is required for its function in TEM. This is the first reported function of IQGAP1 requiring two domains to be present on the same polypeptide. Additionally, we show for the first time that IQGAP1 in the endothelium is required for efficient TEM in vivo. These findings reveal a novel function for IQGAP1 and demonstrate that IQGAP1 in endothelial cells facilitates TEM by directing the LBRC to the site of TEM.

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Citations

Sep 25, 2020·The Journal of Experimental Medicine·Prarthana J DalalWilliam A Muller
Dec 24, 2019·The American Journal of Pathology·Prarthana J DalalDavid P Sullivan
May 1, 2021·Cancers·Yang ZhaoJennifer Gamble

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Methods Mentioned

BETA
GTPase
fluorescence microscopy
confocal microscopy
PCR
immunoprecipitation
fluorescence imaging

Software Mentioned

ImageJ
DeltaVision
Volocity

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