We have discovered that distinct antibodies efficiently trigger a new mechanism of platelet receptor regulation in vivo, namely the ´disintegration´ (uncoupling) of cytoskeleton-connected transmembrane proteins, most notably b3- and b1- integrins, but also GPVI and possibly many more. We postulate that this receptor ‘disintegration’ represents a basic mechanism to regulate platelet adhesiveness and thus provides an interesting target to modulate platelet function. In this project, we will decipher the molecular machinery that mediates integrin- and GPVI-‘disintegration’ in vitro and in vivo by using transgenic mice, super-resolution microscopy and proteomic approaches.