title: Mannose-dependent endoplasmic reticulum (ER)-Golgi intermediate compartment-53-mediated ER to Golgi trafficking of coagulation factors V and VIII.
abstract: The endoplasmic reticulum-Golgi intermediate compartment (ERGIC) is the site of segregation of secretory proteins for anterograde transport, via packaging into COPII-coated transport vesicles. ERGIC-53 is a homo-hexameric transmembrane lectin localized to the ERGIC that exhibits mannose-selective properties in vitro. Null mutations in ERGIC-53 were recently shown to be responsible for the autosomal recessive bleeding disorder, combined deficiency of coagulation factors V and VIII. We have studied the effect of defective ER to Golgi cycling by ERGIC-53 on the secretion of factors V and VIII. The secretion efficiency of factor V and factor VIII was studied in a tetracycline-inducible HeLa cell line overexpressing a wild-type ERGIC-53 or a cytosolic tail mutant of ERGIC-53 (KKAA) that is unable to exit the ER due to mutation of two COOH-terminal phenylalanine residues to alanines. The results show that efficient trafficking of factors V and VIII requires a functional ERGIC-53 cycling pathway and that this trafficking is dependent on post-translational modification of a specific cluster of asparagine (N)-linked oligosaccharides to a fully glucose-trimmed, mannose9 structure.
authors.affiliation: Howard Hughes Medical Institute, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
authors.forename: M
authors.initials: M
authors.lastname: Moussalli
authors.forename: S W
authors.initials: SW
authors.lastname: Pipe
authors.forename: H P
authors.initials: HP
authors.lastname: Hauri
authors.forename: W C
authors.initials: WC
authors.lastname: Nichols
authors.forename: D
authors.initials: D
authors.lastname: Ginsburg
authors.forename: R J
authors.initials: RJ
authors.lastname: Kaufman
mesh_terms: D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005165:Factor V / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism*; D006031:Glycosylation; D006056:Golgi Apparatus / Q000737:chemistry / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008358:Mannose / Q000378:metabolism*; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins / Q000378:metabolism*; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: C084004:LMAN1 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D005165:Factor V; D005169:Factor VIII; D008358:Mannose