IGPR-1 Is Required for Endothelial Cell–Cell Adhesion and Barrier Function. Issue 24 (4th December 2016)

• Record Type: Journal Article
• Authors: Wang, Yun Hwa Walter; Meyer, Rosana D; Bondzie, Philip A; Jiang, Yan; Rahimi, Ida; Rezazadeh, Kobra; Mehta, Manisha; Laver, Nora M.V.; Costello, Catherine E.; Rahimi, Nader
• Is Part Of: Journal of molecular biology. Volume 428:Issue 24:Part B(2016:Dec. 04)
• Page Start: 5019
• Page End: 5033
• Publication Date: 2016-12-04
• Subjects: EC endothelial cell -- CAM cell adhesion molecule -- Ig-CAMs Ig-like cell adhesion proteins -- IGPR-1 Ig-containing and proline-rich receptor-1 -- PAE porcine aortic endothelial -- VE-cadherin vascular endothelial cadherin -- HUVEC human primary umbilical vein EC -- IGPR-1/PAE PAE cells ectopically expressing IGPR-1 -- TEER transendothelial electrical resistance -- GST glutathione S-transferase -- GST-E-IGPR-1 GST fusion extracellular domain of IGPR-1 -- LPS lipopolysaccharide -- ΔN-IGPR-1 extracellular domain deleted IGPR-1 -- β-ME β-mercaptoethanol -- BS3 bis(sulfosuccinimidyl)suberate -- IGPR-1-c-Myc C-terminal c-Myc tagged IGPR-1 -- IGPR-1-FLAG C-terminal FLAG tagged IGPR-1 -- GFP green fluorescent protein -- IGPR-1/GFP-PAE GFP-PAE cells expressing IGPR-1 cell line -- MS mass spectrometry -- LC–MS/MS liquid chromatography–tandem mass spectrometry -- anti-pSer220 polyclonal anti-phospho-Ser220-specific antibody -- MC methycellulose -- cIGPR-1 chimeric IGPR-1 -- CSF-1R colony-stimulating growth factor-1 receptor -- DMEM Dulbecco's modified Eagle's medium; cell adhesion molecule -- IGPR-1 -- endothelial cell barrier function -- angiogenesis; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2016.11.003
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Endothelial cell (EC) barrier function plays a prevalent regulatory mechanism for the integrity and homeostasis of blood vessels and modulates angiogenesis and immune responses. Cell adhesion molecules (CAMs) play a central role in the barrier function of ECs. Although Ig-containing and proline-rich receptor-1(IGPR-1) was recently identified as a novel CAM expressed in ECs, the molecular mechanisms underlying the function of IGPR-1 in ECs remain uncharacterized. In this report, we investigated the role of IGPR-1 in EC barrier function and the molecular mechanism of its activation in ECs. We demonstrate that IGPR-1 is localized to endothelial adherens junctions and, through trans -homophilic dimerization, regulates endothelial cell–cell adhesion and barrier function. Trans -homophilic dimerization of IGPR-1 stimulates the phosphorylation of serine 220 (Ser220), which is required for IGPR-1 to regulate endothelial barrier function and angiogenesis. Moreover, IGPR-1 chimera, which mimics the trans -homophilic dimerization of IGPR-1, induced a sustained phosphorylation of Ser220 upon stimulation with a ligand. Coordinated dimerization of IGPR-1 and its homophilic interaction modulates its adhesive function and Ser220 phosphorylation. This adhesive function of IGPR-1 contributes to the barrier function of ECs. Graphical Abstract: Highlights: Molecular mechanisms of endothelial cell–cell adhesion and barrier function are not fully understood. IGPR-1 is a novel CAM expressed in ECs and is localized to endothelial adherens junctions. IGPR-1through trans -homophilic dimerization regulates endothelial cell–cell adhesion and barrier. Trans -homophilic dimerization of IGPR-1 stimulates the phosphorylation of Ser220, which is required for IGPR-1 to stimulate endothelial barrier function and angiogenesis.