Cyclophilin B trafficking through the secretory pathway is altered by binding of cyclosporin 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.
Price
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Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
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Lim
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Pati
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Walsh
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McKeon
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D000591:Amino Acid Isomerases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D018833:Chaperonins; D006224:Cricetinae; D021983:Cyclophilins; D016572:Cyclosporine / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry; D019696:Peptidylprolyl Isomerase; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D010455:Peptides; D011506:Proteins; C081786:cyclophilin B; D016572:Cyclosporine; D018833:Chaperonins; D000591:Amino Acid Isomerases; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase