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

First Author  Sullivan DP Year  2019
Journal  J Exp Med Volume  216
Issue  11 Pages  2582-2601
PubMed ID  31395618 Mgi Jnum  J:282184
Mgi Id  MGI:6378905 Doi  10.1084/jem.20190008
Citation  Sullivan DP, et al. (2019) Endothelial IQGAP1 regulates leukocyte transmigration by directing the LBRC to the site of diapedesis. J Exp Med 216(11):2582-2601
abstractText  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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