Apical and non-polarized secretion of serpins from MDCK cells

Corticosteroid binding globulin, a member of the serpin family, was previou sly shown to be secreted mainly apically from MDCK cells in an N-glycan ind ependent 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 si gnal. In the present study me have expressed four other members of the serp in family: alpha 1-antitrypsin, C1 inhibitor, plasminogen activator inhibit or-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, alpha 1-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 f our serpins are transported along the exocytotic pathway in an uncomplicate d 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, alpha 1-antitrypsin and C1 inhi bitor are secreted mainly apically from MDCK cells whereas plasminogen acti vator inhibitor-1 and antithrombin are secreted in a non-polarized manner. (C) 2000 Federation of European Biochemical Societies.