Journal article

Translocation of endothelial nitric-oxide synthase involves a ternary complex with caveolin-1 and NOSTRIN


Authors listSchilling, Kirstin; Opitz, Nils; Wiesenthal, Anja; Oess, Stefanie; Tikkanen, Ritva; Müller-Esterl, Werner; Icking, Ann

Publication year2006

Pages3870-3880

JournalMolecular Biology of the Cell

Volume number17

Issue number9

ISSN1059-1524

eISSN1939-4586

DOI Linkhttps://doi.org/10.1091/mbc.E05-08-0709

PublisherAmerican Society for Cell Biology


Abstract
Recently, we characterized a novel endothelial nitric-oxide synthase (eNOS)-interacting protein, NOSTRIN (for eNOS-trafficking inducer), which decreases eNOS activity upon overexpression and induces translocation of eNOS away from the plasma membrane. Here, we show that NOSTRIN directly binds to caveolin-1, a well-established inhibitor of eNOS. Because this interaction occurs between the N terminus of caveolin (positions 1-61) and the central domain of NOSTRIN (positions 323-434), it allows for independent binding of each of the two proteins to eNOS. Consistently, we were able to demonstrate the existence of a ternary complex of NOSTRIN, eNOS, and caveolin-1 in Chinese hamster ovary (CHO)-eNOS cells. In human umbilical vein endothelial cells (HUVECs), the ternary complex assembles at the plasma membrane upon confluence or thrombin stimulation. In CHO-eNOS cells, NOSTRIN-mediated translocation of eNOS involves caveolin in a process most likely representing caveolar trafficking. Accordingly, trafficking of NOSTRIN/eNOS/ caveolin is affected by altering the state of actin filaments or cholesterol levels in the plasma membrane. During caveolar trafficking, NOSTRIN functions as an adaptor to recruit mediators such as dynamin-2 essential for membrane fission. We propose that a ternary complex between NOSTRIN, caveolin-1, and eNOS mediates translocation of eNOS, with important implications for the activity and availability of eNOS in the cell.



Citation Styles

Harvard Citation styleSchilling, K., Opitz, N., Wiesenthal, A., Oess, S., Tikkanen, R., Müller-Esterl, W., et al. (2006) Translocation of endothelial nitric-oxide synthase involves a ternary complex with caveolin-1 and NOSTRIN, Molecular Biology of the Cell, 17(9), pp. 3870-3880. https://doi.org/10.1091/mbc.E05-08-0709

APA Citation styleSchilling, K., Opitz, N., Wiesenthal, A., Oess, S., Tikkanen, R., Müller-Esterl, W., & Icking, A. (2006). Translocation of endothelial nitric-oxide synthase involves a ternary complex with caveolin-1 and NOSTRIN. Molecular Biology of the Cell. 17(9), 3870-3880. https://doi.org/10.1091/mbc.E05-08-0709


Last updated on 2025-25-07 at 11:04