Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/87202
Title: Cavin-2 regulates the activity and stability of endothelial nitric-oxide synthase (eNOS) in angiogenesis
Authors: Boopathy, Gandhi T. K.
Kulkarni, Madhura
Ho, Sze Yuan
Chua, Edmond Wei Min
Boey, Adrian
Barathi, Veluchamy A.
Carney, Tom J.
Wang, Xiaomeng
Hong, Wanjin
Keywords: Angiogenesis
Cell Biology
Issue Date: 2017
Source: Boopathy, G. T. K., Kulkarni, M., Ho, S. Y., Boey, A., Chua, E. W. M., Barathi, V. A., et al. (2017). Cavin-2 regulates the activity and stability of endothelial nitric-oxide synthase (eNOS) in angiogenesis. Journal of Biological Chemistry, 292(43), 17760-17776.
Series/Report no.: Journal of Biological Chemistry
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.
URI: https://hdl.handle.net/10356/87202
http://hdl.handle.net/10220/44347
ISSN: 0021-9258
DOI: http://dx.doi.org/10.1074/jbc.M117.794743
Rights: © 2017 American Society for Biochemistry and Molecular Biology (ASBMB). This paper was published in Journal of Biological Chemistry and is made available as an electronic reprint (preprint) with permission of American Society for Biochemistry and Molecular Biology (ASBMB). The published version is available at: [http://dx.doi.org/10.1074/jbc.M117.794743]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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