The COPII Pathway and Hematologic Disease

Abstract

AbstractAbstract SCI-18Combined deficiency of factor V and factor VIII is a rare autosomal recessive bleeding disorder associated with coordinately decreased levels of two key blood coagulation factors. Genetic studies of affected families identified a novel pathway for the selective transport of a subset of secreted proteins, including factors V and VIII, from the ER to the Golgi. Patients with this disorder carry mutations in one of two components of this pathway, LMAN1 or MCFD2, which together form a receptor for the recruitment of specific cargo to the COPII vesicle for export from the ER. Mutations in other COPII components have recently been identified in other human genetic disorders, including deficiency of SEC23B in patients with congenital dyserythropoietic anemia type II. The molecular pathogenesis of these disorders will be discussed, along with the insights these findings have provided into the function of the mammalian COPII pathway. Disclosures:No relevant conflicts of interest to declare.