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

Journal of molecular and cellular cardiology 2015 Oct

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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 Ca(2+)-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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Citation

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. CAT-1 as a novel CAM stabilizes endothelial integrity and mediates the protective actions of L-Arg via a NO-independent mechanism. Journal of molecular and cellular cardiology. 2015 Oct;87:180-91