THE IMMUNOPHILINS, FK506 BINDING-PROTEIN AND CYCLOPHILIN, ARE DISCRETELY LOCALIZED IN THE BRAIN - RELATIONSHIP TO CALCINEURIN

The immunosuppressant drugs cyclosporin A and FK506 bind to small, pre dominantly soluble proteins cyclophilin and FK506 binding protein, res pectively, to mediate their pharmacological actions. The immunosuppres sant actions of these drugs occur through binding of cyclophilin-cyclo sporin A and FK506 binding protein-FK506 complexes to the calcium-calm odulin-dependent protein phosphatase, calcineurin, inhibiting phosphat ase activity. Utilizing immunohistochemistry, in situ hybridization an d autoradiography, we have localized protein and messenger RNA for FK5 06 binding protein, cyclophilin and calcineurin. All three proteins an d/or messages exhibit a heterogenous distribution through the brain an d spinal cord, with the majority of the localizations being neuronal. We observe a striking co-localization of FK506 binding protein and cal cineurin in most brain regions and a close similarity between calcineu rin and cyclophilin. FK506 binding protein and cyclophilin localizatio ns largely correspond to those of calcineurin, although cyclophilin is enriched in some brain areas that lack calcineurin. The dramatic simi larities in localization of FK506 binding proteins and cyclophilins wi th calcineurin suggest related functions.