IGPR-1 Is Required for Endothelial Cell-Cell Adhesion and Barrier Function

JOURNAL OF MOLECULAR BIOLOGY

卷:428

Article

Wang, Yun Hwa Walter¹  Meyer, Rosana D.¹  Bondzie, Philip A.¹  Jiang, Yan^2,3  Rahimi, Ida¹  Rezazadeh, Kobra¹  Mehta, Manisha¹  Laver, Nora M. V.⁴  Costello, Catherine E.^2,3  Rahimi, Nader¹ 

[1] Boston Univ, Dept Pathol, Sch Med, Boston, MA 02118 USA

[2] Boston Univ, Dept Biochem, Boston, MA 02118 USA

[3] Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Boston, MA 02118 USA

[4] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02116 USA

关键词: cell adhesion molecule;    IGPR-1;    endothelial cell barrier function;    angiogenesis;   

DOI  :  10.1016/j.jmb.2016.11.003

来源: Elsevier

【 摘 要 】

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. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

Free