Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux

Andrew M. Cameron, Joseph P. Steiner, A. Jane Roskams, Siraj M. Ali, Gabriele V. Ronnettt, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review


The immunosuppressant drug FK506 binds to the immunophilin protein FKBP12 and inhibits its prolyl isomerase activity. Immunosuppresive actions, however, are mediated via an FK506-FKBP12 inhibition of the Ca2+-activated phosphatase calcineurin. Physiologic cellular roles for FKBP12 have remained unclear. FKBP12 is physically associated with the RyR and IP3R Ca2+ channels in the absence of FK506, with added FK506 disrupting these complexes. Dissociation of FKBP12 results in alteration of channel Ca2+ conductance in both cases. We now report that calcineurin is physiologically associated with the IP3R-FKBP12 and RyR-FKBP12 receptor complexes and that this interaction can be disrupted by FK506 or rapamycin. Calcineurin anchored to the IP3R via FKBP12 regulates the phosphorylation status of the receptor, resulting in a dynamic Ca2+-sensitive regulation of IP3-mediated Ca2+ flux.

Original languageEnglish (US)
Pages (from-to)463-472
Number of pages10
Issue number3
StatePublished - Nov 3 1995

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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