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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2582-2601 |
| Number of pages | 20 |
| Journal | Journal of Experimental Medicine |
| Volume | 216 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2019 |
Funding
This work was supported by the National Institutes of Health (grant F32 AI084454 to D.P. Sullivan; grants R01 HL046849, R21 HL102519, and R37 HL064774 to W.A. Muller; and grants F30 HL134202 and T32 GM8152 to P.J. Dalal), an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship (to P.J. Dalal), the National Institutes of Health Intramural Research Program funding (D.B. Sacks), and National Institutes of Health National Institute of General Medical Sciences grant R01 GM087575 (to G. Kreitzer).
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology