Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation
Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X.
American Society of Hematology (ASH)
Published 2018
American Society of Hematology (ASH)
Published 2018
| Publication Date: |
2018-08-03
|
|---|---|
| Publisher: |
American Society of Hematology (ASH)
|
| Print ISSN: |
0006-4971
|
| Electronic ISSN: |
1528-0020
|
| Topics: |
Biology
Medicine
|
| Keywords: |
Platelets and Thrombopoiesis, Thrombosis and Hemostasis
|
| Published by: |
| _version_ | 1836399020283527168 |
|---|---|
| autor | Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X. |
| beschreibung | 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 β 3 –/– platelets or by integrin antagonists. The impaired MV release and PS exposure in β 3 –/– platelets were rescued by expression of wild-type β 3 but not a Gα 13 binding–deficient β 3 mutant (E 733 EE to AAA), which blocks outside-in signaling but not ligand binding. Inhibition of Gα 13 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 Gα 13 -integrin interaction, suggesting that Gα 13 -dependent transmission of mechanical signals by integrins induces PS exposure. Inhibition of Gα 13 delayed coagulation in vitro. Furthermore, inhibition or platelet-specific knockout of Gα 13 diminished laser-induced intravascular fibrin formation in arterioles in vivo. Thus, β 3 integrins serve as a shear sensor activating the Gα 13 -dependent outside-in signaling pathway to facilitate platelet procoagulant function. Pharmacological targeting of Gα 13 -integrin interaction prevents occlusive thrombosis in vivo by inhibiting both coagulation and platelet thrombus formation. |
| citation_standardnr | 6313517 |
| datenlieferant | ipn_articles |
| feed_id | 310 |
| feed_publisher | American Society of Hematology (ASH) |
| feed_publisher_url | http://www.hematology.org/ |
| insertion_date | 2018-08-03 |
| journaleissn | 1528-0020 |
| journalissn | 0006-4971 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | American Society of Hematology (ASH) |
| quelle | Blood |
| relation | http://www.bloodjournal.org/cgi/content/short/132/5/533?rss=1 |
| schlagwort | Platelets and Thrombopoiesis, Thrombosis and Hemostasis |
| search_space | articles |
| shingle_author_1 | Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X. |
| shingle_author_2 | Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X. |
| shingle_author_3 | Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X. |
| shingle_author_4 | Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X. |
| shingle_catch_all_1 | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation Platelets and Thrombopoiesis, Thrombosis and Hemostasis 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 β 3 –/– platelets or by integrin antagonists. The impaired MV release and PS exposure in β 3 –/– platelets were rescued by expression of wild-type β 3 but not a Gα 13 binding–deficient β 3 mutant (E 733 EE to AAA), which blocks outside-in signaling but not ligand binding. Inhibition of Gα 13 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 Gα 13 -integrin interaction, suggesting that Gα 13 -dependent transmission of mechanical signals by integrins induces PS exposure. Inhibition of Gα 13 delayed coagulation in vitro. Furthermore, inhibition or platelet-specific knockout of Gα 13 diminished laser-induced intravascular fibrin formation in arterioles in vivo. Thus, β 3 integrins serve as a shear sensor activating the Gα 13 -dependent outside-in signaling pathway to facilitate platelet procoagulant function. Pharmacological targeting of Gα 13 -integrin interaction prevents occlusive thrombosis in vivo by inhibiting both coagulation and platelet thrombus formation. Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X. American Society of Hematology (ASH) 0006-4971 00064971 1528-0020 15280020 |
| shingle_catch_all_2 | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation Platelets and Thrombopoiesis, Thrombosis and Hemostasis 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 β 3 –/– platelets or by integrin antagonists. The impaired MV release and PS exposure in β 3 –/– platelets were rescued by expression of wild-type β 3 but not a Gα 13 binding–deficient β 3 mutant (E 733 EE to AAA), which blocks outside-in signaling but not ligand binding. Inhibition of Gα 13 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 Gα 13 -integrin interaction, suggesting that Gα 13 -dependent transmission of mechanical signals by integrins induces PS exposure. Inhibition of Gα 13 delayed coagulation in vitro. Furthermore, inhibition or platelet-specific knockout of Gα 13 diminished laser-induced intravascular fibrin formation in arterioles in vivo. Thus, β 3 integrins serve as a shear sensor activating the Gα 13 -dependent outside-in signaling pathway to facilitate platelet procoagulant function. Pharmacological targeting of Gα 13 -integrin interaction prevents occlusive thrombosis in vivo by inhibiting both coagulation and platelet thrombus formation. Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X. American Society of Hematology (ASH) 0006-4971 00064971 1528-0020 15280020 |
| shingle_catch_all_3 | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation Platelets and Thrombopoiesis, Thrombosis and Hemostasis 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 β 3 –/– platelets or by integrin antagonists. The impaired MV release and PS exposure in β 3 –/– platelets were rescued by expression of wild-type β 3 but not a Gα 13 binding–deficient β 3 mutant (E 733 EE to AAA), which blocks outside-in signaling but not ligand binding. Inhibition of Gα 13 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 Gα 13 -integrin interaction, suggesting that Gα 13 -dependent transmission of mechanical signals by integrins induces PS exposure. Inhibition of Gα 13 delayed coagulation in vitro. Furthermore, inhibition or platelet-specific knockout of Gα 13 diminished laser-induced intravascular fibrin formation in arterioles in vivo. Thus, β 3 integrins serve as a shear sensor activating the Gα 13 -dependent outside-in signaling pathway to facilitate platelet procoagulant function. Pharmacological targeting of Gα 13 -integrin interaction prevents occlusive thrombosis in vivo by inhibiting both coagulation and platelet thrombus formation. Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X. American Society of Hematology (ASH) 0006-4971 00064971 1528-0020 15280020 |
| shingle_catch_all_4 | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation Platelets and Thrombopoiesis, Thrombosis and Hemostasis 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 β 3 –/– platelets or by integrin antagonists. The impaired MV release and PS exposure in β 3 –/– platelets were rescued by expression of wild-type β 3 but not a Gα 13 binding–deficient β 3 mutant (E 733 EE to AAA), which blocks outside-in signaling but not ligand binding. Inhibition of Gα 13 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 Gα 13 -integrin interaction, suggesting that Gα 13 -dependent transmission of mechanical signals by integrins induces PS exposure. Inhibition of Gα 13 delayed coagulation in vitro. Furthermore, inhibition or platelet-specific knockout of Gα 13 diminished laser-induced intravascular fibrin formation in arterioles in vivo. Thus, β 3 integrins serve as a shear sensor activating the Gα 13 -dependent outside-in signaling pathway to facilitate platelet procoagulant function. Pharmacological targeting of Gα 13 -integrin interaction prevents occlusive thrombosis in vivo by inhibiting both coagulation and platelet thrombus formation. Pang, A., Cui, Y., Chen, Y., Cheng, N., Delaney, M. K., Gu, M., Stojanovic-Terpo, A., Zhu, C., Du, X. American Society of Hematology (ASH) 0006-4971 00064971 1528-0020 15280020 |
| shingle_title_1 | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation |
| shingle_title_2 | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation |
| shingle_title_3 | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation |
| shingle_title_4 | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation |
| timestamp | 2025-06-30T23:36:19.830Z |
| titel | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation |
| titel_suche | Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation |
| topic | W WW-YZ |
| uid | ipn_articles_6313517 |