CONTROL OF A NOVEL ADENYLYL-CYCLASE BY CALCINEURIN

The molecular complex formed by the immunosuppressant FK506 and the im munophilin protein FKBP12 potently inhibits the Ca2+/calmodulin-activa ted protein phosphatase calcineurin. This mechanism appears to be comm on to all types of cell, implying that fundamental physiological modes of calcineurin regulation are exploited by immunosuppressants. The pr esent paper describes a novel adenylyl cyclase regulated by calcineuri n that contains an FKBP12-like domain and may thus constitute a physio logically relevant calcineurin docking site mimicked by immunosuppress ant-immunophilin complexes. The enzyme messenger RNA is particularly e nriched in the cerebral cortex, striatum and hippocampus, where it is localized to neuronal perikarya, indicative of an important role in ne uronal function. (C) 1995 Academic Press, Inc.