title: Fibrinogen assembly: insights from chicken hepatocytes.
abstract: In all vertebrate species studied, the complex, disulfide-linked structure of fibrinogen is essentially the same: a hexamer assembled from three different subunits (A alpha, B beta, gamma)2. This study utilized species differences in fibrinogen subunit monomer pools to address the question of how these surplus subunit pools may affect the assembly process. We used a chicken model system in which B beta and gamma-subunits are present in excess, in contrast to the A alpha and gamma-subunit surplus found in human model systems. Analysis was based on pulse-chase experiments with electrophoretic separation of intracellular forms and secreted fibrinogen on reducing and nonreducing gels. The chicken liver-derived cells employed for this purpose, primary hepatocytes and a hepatoma cell line with a fortuitous defect in fibrinogen synthesis, together offer advantages over human systems for resolving the complexes formed in the early stages of assembly. The results demonstrate that in chicken hepatocytes there is an initial binding of gamma to A alpha subunits rather than to B beta subunits, as occurs in human hepatoma cells. Nevertheless, the presence of similar intracellular fibrinogen-related forms in both chicken- and human-derived cells, in the context of their differing subunit monomer pools, suggests an assembly pathway common to both species, with the versatility to be regulated by limitation of A alpha or B beta subunit production.
authors.affiliation: Lindsley F. Kimball Research Institute of the New York Blood Center, New York 10021.
authors.forename: C
authors.initials: C
authors.lastname: Oddoux
authors.forename: G
authors.initials: G
authors.lastname: Grieninger
mesh_terms: D000818:Animals; D002645:Chickens; D005340:Fibrinogen / Q000737:chemistry / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D012016:Reference Values; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D005340:Fibrinogen