Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation.

Blood
Aiming PangXiaoping Du

Abstract

It is currently unclear why agonist-stimulated platelets require shear force to efficiently externalize the procoagulant phospholipid phosphatidylserine (PS) and release PS-exposed microvesicles (MVs). We reveal that integrin outside-in signaling is an important mechanism for this requirement. PS exposure and MV release were inhibited in β3-/- platelets or by integrin antagonists. The impaired MV release and PS exposure in β3-/- platelets were rescued by expression of wild-type β3 but not a Gα13 binding-deficient β3 mutant (E733EE to AAA), which blocks outside-in signaling but not ligand binding. Inhibition of Gα13 or Src also diminished agonist/shear-dependent PS exposure and MV release, further indicating a role for integrin outside-in signaling. PS exposure in activated platelets was induced by application of pulling force via an integrin ligand, which was abolished by inhibiting Gα13-integrin interaction, suggesting that Gα13-dependent transmission of mechanical signals by integrins induces PS exposure. Inhibition of Gα13 delayed coagulation in vitro. Furthermore, inhibition or platelet-specific knockout of Gα13 diminished laser-induced intravascular fibrin formation in arterioles in vivo. Thus, β3 integrins serve as a shea...Continue Reading

References

Dec 1, 1975·British Journal of Haematology·J Vecchione, M B Zucker
Dec 1, 1974·The Journal of Clinical Investigation·J Niemetz, A J Marcus
Dec 7, 1983·Biochimica Et Biophysica Acta·E M BeversR F Zwaal
Apr 1, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·P A HolmeK S Sakariassen
Oct 4, 2003·Science·Seiji TadokoroDavid A Calderwood
Oct 7, 2003·Nature Medicine·Alexandra MoersStefan Offermanns
Nov 1, 2003·Proceedings of the National Academy of Sciences of the United States of America·Elena G Arias-SalgadoSanford J Shattil
Jun 19, 2004·Blood·Sanford J Shattil, Peter J Newman
Aug 16, 2005·Current Opinion in Cell Biology·Mark H GinsbergSanford J Shattil
Dec 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Erik R VandendriesBarbara C Furie
Oct 31, 2007·The Journal of Cell Biology·Panagiotis FlevarisXiaoping Du
Feb 19, 2008·Nature Medicine·Markus MoserReinhard Fässler
May 7, 2008·The Journal of Cell Biology·Yan-Qing MaEdward F Plow
Jul 1, 2009·The Journal of Cell Biology·Fang KongCheng Zhu
Aug 3, 2010·Blood·Ben T AtkinsonBarbara C Furie
Nov 13, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Zhenyu LiXiaoping Du
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·F YeM H Ginsberg
Sep 26, 2012·Journal of Thrombosis and Haemostasis : JTH·L V M Rao, U R Pendurthi
Apr 13, 2013·Circulation Research·Kamila BledzkaEdward F Plow
Feb 28, 2014·Thrombosis and Haemostasis·Julia E Geddings, Nigel Mackman
May 30, 2014·Blood·Lacramioara IvanciuRodney M Camire
Oct 7, 2015·Trends in Cell Biology·Katsumori Segawa, Shigekazu Nagata
Jul 18, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Yunfeng ChenCheng Zhu
Feb 24, 2017·Physiology·Brian Estevez, Xiaoping Du

❮ Previous
Next ❯

Citations

Aug 4, 2018·Blood·Jerry Ware
Feb 23, 2019·Journal of the American Heart Association·Keziah R HernandezFadi T Khasawneh
May 17, 2019·Leukemia & Lymphoma·Hind RafeiElias J Jabbour
Jan 15, 2020·Blood Advances·Nima AbbasianMatthew T Harper
Mar 21, 2020·Frontiers in Cardiovascular Medicine·Emily C Reddy, Margaret L Rand
Sep 6, 2020·Journal of Hematology & Oncology·Si ZhangLiang Hu
May 11, 2019·Biophysics Reviews·Yunfeng ChenLining Arnold Ju
Jun 13, 2020·Journal of Thrombosis and Thrombolysis·Diana A Gorog, Richard C Becker
Mar 12, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Zheng XuXiaoping Du
May 29, 2021·Nature Communications·Ni ChengXiaoping Du
Aug 6, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Jiaxin ZhaoXiaoxiang Yan
Jun 30, 2021·Current Opinion in Hematology·Frederik DenormeRobert A Campbell
Oct 1, 2021·Journal of Thrombosis and Haemostasis : JTH·Nadine Martins CastanheiraHermann Schillers
Nov 21, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claire W ChangXiaoping Du

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aneurysm

Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.

Blood Coagulation Signaling Pathways

Coagulation is the process by which a blood clot is formed. This process includes both the formation of a platelet plug as well as a cascade of clotting factors resulting in the formation of fibrin strands. Find the latest research on coagulation signaling pathways here.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Aortic Aneurysm

An aortic aneurysm is the weakening and bulging of the blood vessel wall in the aorta. This causes dilatation of the aorta, which is usually asymptomatic but carries the risk of rupture and hemorrhage. Find the latest research on aortic aneurysms here.