Apical and non-polarized secretion of serpins from MDCK cells

Corticosteroid binding globulin, a member of the serpin family, was previously shown to be secreted mainly apically from MDCK cells in an N-glycan independent manner [Larsen et al. (1999) FEBS Lett. 451, 19-22]. Apart from N-glycosylation, serpins are not known to carry any other posttranslational modifications, suggesting the presence of a proteinaceous apical sorting signal. In the present study we have expressed four other members of the serpin family: alpha1-antitrypsin, C1 inhibitor, plasminogen activator inhibitor-1 and antithrombin in MDCK cells. Tight monolayers of transfected cells were grown on filters and the amounts of recombinantly expressed serpins in the apical and the basolateral media were determined. alpha1-Antitrypsin and C1 inhibitor were found mainly in the apical medium whereas plasminogen activator inhibitor-1 and antithrombin were found in roughly equal amounts in the apical and basolateral media. Control experiments showed that all four serpins are transported along the exocytotic pathway in an uncomplicated way that does not involve transcytosis or differences in stability on the two sides of the cells. We conclude that some members of the serpin family including corticosteroid binding globulin, alpha1-antitrypsin and C1 inhibitor are secreted mainly apically from MDCK cells whereas plasminogen activator inhibitor-1 and antithrombin are secreted in a non-polarized manner.