cGMP signaling inhibits platelet shape change through regulation of the RhoA-Rho Kinase-MLC phosphatase signaling pathway

Journal of Thrombosis and Haemostasis : JTH
Ahmed AburimaKhalid M Naseem

Abstract

Essentials Platelet shape change requires cytoskeletal rearrangement via myosin-mediated actin contraction. We investigated whether nitric oxide (NO) affected thrombin-induced platelet shape change. NO inhibits shape change, RhoA/ROCK signalling and myosin light chain (MLC) phosphorylation. NO promotes MLC phosphatase activity, thus prevents MLC phosphorylation and shape change. Background Platelet shape change, spreading and thrombus stability require activation of the actin cytoskeleton contractile machinery. The mechanisms controlling actin assembly to prevent unwanted platelet activation are unclear. Objectives We examined the effects of nitric oxide on the signaling pathways regulating platelet actin-myosin activation. Results S-nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and myosin phosphorylation of the myosin light chain (MLC). Because thrombin stimulates phospho-MLC through the RhoA/ ROCK dependent inhibition of MLC phosphatase (MLCP) we examined the effects of NO on this pathway. Thrombin caused the GTP loading and activation of RhoA, leading to the ROCK-mediated phosphorylation of MLCP on threonine 853 (thr853 ), which is known to inhibit phosphatase activity. Treatment of platelets wit...Continue Reading

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Citations

Oct 21, 2018·Journal of Cellular Physiology·Eunae YouSangmyung Rhee
Jul 27, 2018·Research and Practice in Thrombosis and Haemostasis·Zoltan Nagy, Albert Smolenski
Aug 28, 2020·Canadian Journal of Physiology and Pharmacology·Pierre E Thibeault, Rithwik Ramachandran
Jul 22, 2020·Journal of Thrombosis and Haemostasis : JTH·Shane ComerAlbert Smolenski
May 6, 2021·International Journal of Molecular Sciences·Olga ShevchukAlbert Sickmann
Aug 28, 2021·Cells·Maria Luísa da Silveira Hahmeyer, José Eduardo da Silva-Santos

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