CYCLOPHILIN-B TRAFFICKING THROUGH THE SECRETORY PATHWAY IS ALTERED BY BINDING OF CYCLOSPORINE-A

Cyclophilin B is targeted to the secretory pathway via an endoplasmic reticulum signal sequence. We analyzed the localization and trafficking of endogenous and transfected cyclophilin B In mammalian cells. Cyclophilin B accumulates both in the endoplasmic reticulum and in complexes on the plasma membrane. The immunosuppressant cyclosporin A specifically mobilizes cyclophilin B from the endoplasmic reticulum, and promotes the secretion of cyclophilin B into the medium. We suggest that cyclosporin A competes with endogenous plasma membrane proteins for association with cyclophilin B in the secretory pathway. These findings argue in favor of a role for cyclophilin B as a chaperone to proteins destined for the plasma membrane, rather than solely as a proline isomerase functioning within the endoplasmic reticulum.