Mechanisms of platelet receptor regulation and disintegration (A07)

血小板受体调节和崩解机制（A07）

• 批准号: 406381706
• 金额: --
• 依托单位: Lehrstuhl für Experimentelle Biomedizin
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/406381706?language=en
• 关键词: Mechanisms; platelet; receptor; regulation; disintegration

We have shown that αIIbβ3 together with its associated tetraspanin, CD9, can be irreversibly removed from circulating platelets. The process involves mechanical forces after the ligated integrin is anchored, clustered at the platelet ‘rear edge’ and segregated within a long protrusion or tether. We found clear indications that this flow-dependent deposition of αIIbβ3/CD9-enriched tethers (termed PITTs) contributes to thrombo-inflammation. Next, the detailed molecular basis and pathophysiological significance of PITT formation will be our focus as well as the ‘disintegration’/deposition of other platelet membrane receptors, such as β1-integrins and GPVI in vitro and in vivo.

我们已经证明，αIIbβ3及其相关的四跨膜蛋白CD 9可以不可逆地从循环血小板中清除。该过程涉及在连接的整联蛋白被锚定、聚集在血小板“后边缘”并在长突起或系链内分离之后的机械力。我们发现明确的迹象表明，这种αIIbβ3/CD 9富集系链（称为PITT）的流动依赖性沉积有助于血栓炎症。接下来，详细的分子基础和PITT形成的病理生理学意义将是我们的重点，以及其他血小板膜受体，如β1-整合素和GPVI在体外和体内的“解体”/沉积。