The storage defects in grey platelet syndrome and αδ-storage pool deficiency affect α-granule factor V and multimerin storage without altering their proteolytic processing

Among proteins stored in alpha -granules, multimerin and factor V share unusual features: they bind to each other, are proteolysed to unique forms and are stored eccentrically in alpha -granules. These unique features of their processing led us to study these proteins in alpha delta storage pool deficiency (alpha delta -SPD) and grey platelet syndrome (GPS, alpha -SPD), two conditions known to impair alpha -granule protein storage. Platelet factor V and multimerin were severely reduced in GPS, whereas they ranged from reduced to normal in alpha delta -SPD. The platelet levels of factor V and multimerin in these disorders indicated multimerin deficiency was not predictive of platelet factor V deficiency, although it reduced the amount of multimerin associated with platelet factor V, In GPS only, the defect in storing proteins was associated with increased multimerin and multimerin-factor V complexes in plasma. Like normal platelets, GPS and alpha delta -SPD platelets contained factor V mainly in granules. Platelet factor V and multimerin were proteolysed to normal platelet forms in GPS and alpha delta -SPD platelets, indicating that these conditions preserve some aspects of normal alpha -granule protein processing. Although we found factor V can be stored in platelets deficient in multimerin, our data indicate that multimerin storage influences the point at which multimerin binds factor V.