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Endothelial IQGAP1 regulates leukocyte transmigration by directing the LBRC to the site of diapedesis.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-08-08 , DOI: 10.1084/jem.20190008 David P Sullivan 1 , Prarthana J Dalal 1 , Fanny Jaulin 2 , David B Sacks 3 , Geri Kreitzer 4 , William A Muller 5
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-08-08 , DOI: 10.1084/jem.20190008 David P Sullivan 1 , Prarthana J Dalal 1 , Fanny Jaulin 2 , David B Sacks 3 , Geri Kreitzer 4 , William A Muller 5
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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.
中文翻译：
内皮IQGAP1通过将LBRC引导至尿布分离位点来调节白细胞的迁移。
白细胞跨内皮迁移（TEM）对炎症至关重要。在内皮中，TEM需要协调膜的运动和细胞骨架的相互作用，包括显着地募集侧边界回收室（LBRC）。最近在筛查LBRC相互作用蛋白的过程中鉴定了支架蛋白IQGAP1。击倒内皮IQGAP1破坏了LBRC的定向运动并显着降低了白细胞TEM。截短的IQGAP1构建体的表达表明，IQGAP1定位到内皮边界需要钙黄素同源结构域，并且同一IQGAP1多肽上的IQ结构域是其在TEM中的功能所必需的。这是IQGAP1的第一个报告功能，要求在同一多肽上存在两个域。此外，我们首次显示内皮中的IQGAP1是体内有效TEM所必需的。这些发现揭示了IQGAP1的新功能，并证明内皮细胞中的IQGAP1通过将LBRC引导至TEM部位来促进TEM。
更新日期：2019-11-04
中文翻译：
内皮IQGAP1通过将LBRC引导至尿布分离位点来调节白细胞的迁移。
白细胞跨内皮迁移（TEM）对炎症至关重要。在内皮中，TEM需要协调膜的运动和细胞骨架的相互作用，包括显着地募集侧边界回收室（LBRC）。最近在筛查LBRC相互作用蛋白的过程中鉴定了支架蛋白IQGAP1。击倒内皮IQGAP1破坏了LBRC的定向运动并显着降低了白细胞TEM。截短的IQGAP1构建体的表达表明，IQGAP1定位到内皮边界需要钙黄素同源结构域，并且同一IQGAP1多肽上的IQ结构域是其在TEM中的功能所必需的。这是IQGAP1的第一个报告功能，要求在同一多肽上存在两个域。此外，我们首次显示内皮中的IQGAP1是体内有效TEM所必需的。这些发现揭示了IQGAP1的新功能，并证明内皮细胞中的IQGAP1通过将LBRC引导至TEM部位来促进TEM。
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