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  current news   Press   selected story    
     
  27 October 2017  
 
Cavin-2 regulates the activity and stability of endothelial nitric-oxide synthase (eNOS) in angiogenesis
 
 




Authors
Gandhi T. K. Boopathy‡§1, Madhura Kulkarni, Sze Yuan Ho, Adrian Boey, Edmond Wei Min Chua,
Veluchamy A. Barathi§**‡‡, Tom J. Carney‡§¶, Xiaomeng Wang‡§¶, and Wanjin Hong‡§2

Author Affiliations
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
Singapore Eye Research Institute (SERI), 20 College Road, 169856 Singapore
**Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, 8 College Rd., 169857 Singapore
‡‡Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
§SERI-IMCB Programme in Retinal Angiogenic Diseases (SIPRAD), SERI-IMCB, Singapore

Published online in The Journal of Biological Chemistry on September 14, 2017

Cavin-2 regulates the activity and stability of endothelial nitric-oxide synthase (eNOS) in angiogenesis
Gandhi T. K. Boopathy, Madhura Kulkarni, Sze Yuan Ho, Adrian Boey, Edmond Wei Min Chua, Veluchamy A. Barathi, Tom J. Carney, Xiaomeng Wang, and Wanjin Hong
J. Biol. Chem. (2017) 292(43) 17760–17776
https://doi.org/10.1074/jbc.M117.794743

 

Abstract
Angiogenesis is a highly regulated process for formation of new blood vessels from pre-existing ones. Angiogenesis is dysregulated in various pathologies, including age-related macular degeneration, arthritis, and cancer. Inhibiting pathological angiogenesis therefore represents a promising therapeutic strategy for treating these disorders, highlighting the need to study angiogenesis in more detail. To this end, identifying the genes essential for blood vessel formation and elucidating their function are crucial for a complete understanding of angiogenesis. Here, focusing on potential candidate genes for angiogenesis, we performed a morpholino-based genetic screen in zebrafish and identified Cavin-2, a membrane-bound phosphatidylserine-binding protein and critical organizer of caveolae (small microdomains in the plasma membrane), as a regulator of angiogenesis. Using endothelial cells, we show that Cavin-2 is required for in vitro angiogenesis and also for endothelial cell proliferation, migration, and invasion. We noted a high level of Cavin-2 expression in the neovascular tufts in the mouse model of oxygen-induced retinopathy, suggesting a role for Cavin-2 in pathogenic angiogenesis. Interestingly, we also found that Cavin-2 regulates the production of nitric oxide (NO) in endothelial cells by controlling the stability and activity of the endothelial nitric-oxide synthase (eNOS) and that Cavin-2 knockdown cells produce much less NO than WT cells. Also, mass spectrometry, flow cytometry, and electron microscopy analyses indicated that Cavin-2 is secreted in endothelial microparticles (EMPs) and is required for EMP biogenesis. Taken together, our results indicate that in addition to its function in caveolae biogenesis, Cavin-2 plays a critical role in endothelial cell maintenance and function by regulating eNOS activity.

Figure

Figure legend
: Scheme of the regulation of nitric oxide (NO) production by Cavin-2 in endothelial cells. The presence of Cavin-2 positively helps in NO production by stabilizing and activating eNOS. The loss of Cavin-2 adversely effects NO production by destabilizing and inactivating eNOS.

For more information on Wanjin HONG's lab, please click here.