title: IGPR-1 Is Required for Endothelial Cell-Cell Adhesion and Barrier Function.
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.
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Yun Hwa Walter
authors.initials: YHW
authors.lastname: Wang
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Rosana D
authors.initials: RD
authors.lastname: Meyer
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Bondzie
authors.affiliation: Department of Biochemistry and Center for Biomedical Mass Spectrometry, School of Medicine, Boston University, Boston, MA, 02118 USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Ida
authors.initials: I
authors.lastname: Rahimi
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Kobra
authors.initials: K
authors.lastname: Rezazadeh
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Mehta
authors.affiliation: Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02116, USA.
authors.forename: Nora M V
authors.initials: NMV
authors.lastname: Laver
authors.affiliation: Department of Biochemistry and Center for Biomedical Mass Spectrometry, School of Medicine, Boston University, Boston, MA, 02118 USA.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: nrahimi@bu.edu.
authors.forename: Nader
authors.initials: N
authors.lastname: Rahimi
mesh_terms: D018106:CD28 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational
chemical_list: D018106:CD28 Antigens; C585279:TMIGD2 protein, human
keywords: IGPR-1; angiogenesis; cell adhesion molecule; endothelial cell barrier function