Mechanosensitive cGMP signalling in platelets (A05)

环核苷酸cGMP是心血管系统的重要信号分子，越来越多地成为临床用药的靶点。我们已经在小鼠和人的血小板中发现了一种机械敏感的cGMP途径，它是由一个膜相关的整合素-cGMP信号体组织的。在这个项目中，我们将研究机械性cGMP的分子结构和作用方式，以及它在小鼠和人类中的功能和治疗意义。我们假设，整合素和cGMP信号之间的新联系提供了一种流动/剪切敏感的破坏机制，以防止血小板相关疾病中的血小板过度活动。

The cyclic nucleotide cGMP is an important signalling molecule of our cardiovascular system and increasingly targeted by clinically used drugs. We have discovered a mechanosensitive cGMP pathway (mechano-cGMP) in mouse and human platelets that is organised by a membrane-associated integrin-cGMP signalosome. In this project, we will study the molecular architecture and mode of action of mechano-cGMP as well as its functional and therapeutic relevance in mouse and human. We hypothesise that the novel link between integrin and cGMP signalling provides a flow/shear-sensitive break mechanism to prevent platelet overactivity in platelet-related disorders.