The role of βγ and αγ complexes in the assembly of human fibrinogen

Abstract

The role of αγ and βγ dimers as intermediates in the assembly of fibrinogen was examined in cell fusion experiments using stably transfected baby hamster kidney cell lines expressing one or combinations of fibrinogen chains. Fibrinogen was readily formed and secreted into the culture media when cells co-expressing β and γ chains and generating βγ complexes were fused with cells expressing only the a chain. Likewise, when cells co- expressing α and γ chains and generating αγ complexes were fused with cells expressing only the β chain, fibrinogen was also formed and secreted. The relative amounts of αγ or βγ intermediates observed during fibrinogen biosynthesis were determined by the levels of the component chains; i.e. when the β chain was limiting, the αγ dimer was the predominant intermediate; likewise, when the α chain was limiting, the βγ complex was the predominant intermediate. The incorporation of preformed αγ and βγ complexes into secreted fibrinogen did not require concurrent protein synthesis, as shown by experiments employing cycloheximide. These data strongly support the role of αγ and βγ complexes as functional intermediates in the assembly of fibrinogen.