biostudies-literatureBaaten CCFMJNHLBI NIH HHS2320-2331https://www.ebi.ac.uk/biostudies/studies/S-EPMC6156892biostudies-literatureUnknown2(18)The platelet receptors glycoprotein Ibα (GPIbα) and GPVI are known to be cleaved by members of a disintegrin and metalloprotease (ADAM) family (ADAM10 and ADAM17), but the mechanisms and consequences of this shedding are not well understood. Our results revealed that (1) glycoprotein shedding is confined to distinct platelet populations showing near-complete shedding, (2) the heterogeneity between (non)shed platelets is independent of agonist type but coincides with exposure of phosphatidylserine (PS), and (3) distinct pathways of shedding are induced by elevated Ca²⁺, low Ca²⁺ protein kinase C (PKC), or apoptotic activation. Furthermore, we found that receptor shedding reduces binding of von Willebrand factor, enhances binding of coagulation factors, and augments fibBlood advancesPlatelet heterogeneity in activation-induced glycoprotein shedding: functional effects.PMC6156892R01 HL071544R01 HL123984Collins PWMastenbroek TGSwieringa FFeijge MAHBaaten CCFMJBock PEDonners MMPCvan der Meijden PEJLi RMisztal THeemskerk JWMfalsePlatelet heterogeneity in activation-induced glycoprotein shedding: functional effects.The platelet receptors glycoprotein Ibα (GPIbα) and GPVI are known to be cleaved by members of a disintegrin and metalloprotease (ADAM) family (ADAM10 and ADAM17), but the mechanisms and consequences of this shedding are not well understood. Our results revealed that (1) glycoprotein shedding is confined to distinct platelet populations showing near-complete shedding, (2) the heterogeneity between (non)shed platelets is independent of agonist type but coincides with exposure of phosphatidylserine (PS), and (3) distinct pathways of shedding are induced by elevated Ca²⁺, low Ca²⁺ protein kinase C (PKC), or apoptotic activation. Furthermore, we found that receptor shedding reduces binding of von Willebrand factor, enhances binding of coagulation factors, and augments fib2018-01-01T00:00:00Z2018 Sep2026-06-07T06:40:20.492Z2019-03-26T23:57:33ZS-EPMC61568923023208510.1182/bloodadvances.2017011544