CAT-1 as a novel CAM stabilizes endothelial integrity and mediates the protective actions of l-Arg via a NO-independent mechanism

Lu Guo, Shuang Tian, Yuguo Chen, Yun Mao, Sumei Cui, Aihua Hu, Jianliang Zhang, Shen Ling Xia, Yunchao Su, Jie Du, Edward R. Block, Xing Li Wang, Zhaoqiang Cui

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Interendothelial junctions play an important role in the maintenance of endothelial integrity and the regulation of vascular functions. We report here that cationic amino acid transporter-1 (CAT-1) is a novel interendothelial cell adhesion molecule (CAM). We identified that CAT-1 protein localized at cell-cell adhesive junctions, similar to the classic CAM of VE-cadherin, and knockdown of CAT-1 with siRNA led to an increase in endothelial permeability. In addition, CAT-1 formed a cis-homo-dimer and showed Ca2+-dependent trans-homo-interaction to cause homophilic cell-cell adhesion. Co-immunoprecipitation assays showed that CAT-1 can associate with β-catenin. Furthermore, we found that the sub-cellular localization and function of CAT-1 are associated with cell confluency, in sub-confluent ECs CAT-1 proteins distribute on the entire surface and function as l-Arg transporters, but most of the CAT-1 in the confluent ECs are localized at interendothelial junctions and serve as CAMs. Further functional characterization has disclosed that extracellular l-Arg exposure stabilizes endothelial integrity via abating the cell junction disassembly of CAT-1 and blocking the cellular membrane CAT-1 internalization, which provides the new mechanisms for l-Arg paradox and trans-stimulation of cationic amino acid transport system (CAAT). These results suggest that CAT-1 is a novel CAM that directly regulates endothelial integrity and mediates the protective actions of l-Arg to endothelium via a NO-independent mechanism.

Original languageEnglish (US)
Pages (from-to)180-191
Number of pages12
JournalJournal of molecular and cellular cardiology
Volume87
DOIs
StatePublished - Oct 1 2015

Keywords

  • CAT-1
  • Cell adhesion molecule
  • L-arginine paradox
  • Trans-stimulation
  • Vascular permeability

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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