{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T23:34:26Z","timestamp":1776987266700,"version":"3.51.4"},"reference-count":41,"publisher":"Georg Thieme Verlag KG","issue":"05","funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81700130"],"award-info":[{"award-number":["81700130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Fund for Distinguished Young Scholars of Hubei Province","award":["2022CFA054"],"award-info":[{"award-number":["2022CFA054"]}]},{"name":"Open Project of the Key Laboratory of Thrombosis and Hemostasis of the National Health Commission","award":["KJS2419"],"award-info":[{"award-number":["KJS2419"]}]},{"name":"The Undergraduate Teaching and Research Project and Graduate Teaching and Research Project of Huazhong University of Science and Technology","award":["2024130, 2025YB015"],"award-info":[{"award-number":["2024130, 2025YB015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>Platelet spreading and clot retraction, albeit both mediated by integrin outside-in signaling, lead to platelet shape changes in two opposite directions. The mechanisms by which these processes are regulated are not fully understood. Our previous study found that E726Q mutation in \u03b23 integrin caused impaired spreading in Chinese hamster ovary (CHO) cells on immobilized fibrinogen.<\/jats:p>\n                  <jats:p>The current study further utilized knock-in mice bearing the \u03b23E726Q mutation to explore the underlying mechanisms whereby the E726 residue differentially influences platelet spreading and clot retraction.<\/jats:p>\n                  <jats:p>Compared to wild type (WT) platelets, \u03b23E726Q platelets displayed similar level of \u03b23 expression but partially impaired fibrinogen binding associated with attenuated responses in platelet aggregation and P-selectin exposure. Notably, \u03b23E726Q mutation resulted in defective platelet spreading but accelerated clot retraction concomitant with increased clot density. Functionally, \u03b23E726Q mice displayed prolonged bleeding time and defective thrombogenesis in vitro and in vivo. Further mechanistic study showed that in \u03b23E726Q platelets the activities of RhoA and Rac1 were significantly enhanced following thrombin stimulation, possibly due to reduced binding of G\u03b113 to the \u03b23 cytoplasmic tail.<\/jats:p>\n                  <jats:p>Taken together, the \u03b23E726 is a potential novel regulatory site that influences the direct interaction of \u03b23 cytoplasmic tail with G\u03b113 and therefore the activity of downstream RhoA, a molecular switch that shifts platelet spreading into clot retraction.<\/jats:p>","DOI":"10.1055\/a-2664-7955","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T23:37:15Z","timestamp":1753400235000},"page":"473-487","source":"Crossref","is-referenced-by-count":0,"title":["Integrin \u03b23E726 Regulates the Switch Between Platelet Spreading and Clot Retraction by Interfering G\u03b113\/RhoA 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijie","family":"Gan","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifei","family":"Ma","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Mao","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiansong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zhejiang Key Laboratory for Precision Diagnosis and Treatment of Hematological Malignancies, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2524-3730","authenticated-orcid":false,"given":"Chao","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, Hubei, China"},{"name":"The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province and Tongji-Rongcheng Center 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