The BioGRID | PUBLICATION VIEW

	J. Thromb. Haemost. Nov (2003); 1(11):2360-7
LMAN1 is a molecular chaperone for the secretion of coagulation factor VIII.
Cunningham MA, Pipe SW, Zhang B, Hauri HP, Ginsburg D, Kaufman RJ
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0650, USA.
Abstract: Combined deficiency of both coagulation factors (F)V and VIII is a rare autosomal recessive bleeding disorder caused by null expression of LMAN1 (previously termed ERGIC-53) in a majority of affected individuals. Previously, a requirement for a functional LMAN1 cycling pathway between the ER and Golgi was demonstrated for efficient secretion of FV and FVIII (Moussalli et al. J Biol Chem 1999; 274: 32569), however, the molecular nature of the interaction between LMAN1 and its cargo was not characterized. Using coimmunoprecipitation of LMAN1 and FVIII from transfected HeLa and COS-1 cells, we demonstrate an interaction between LMAN1 and FVIII in vivo. The interaction was mediated via high mannose-containing asparagine-linked oligosaccharides that are densely situated within the B domain of FVIII, as well as protein-protein interactions. These results are interpreted based on the recent determination of the crystal structure of the carbohydrate recognition domain of LMAN1.
[PUBMED: 14629470]