Physiological Reviews, Vol 76, 631-649, Copyright © 1996 by American Physiological Society

JOURNAL ARTICLE

Cellular functions of immunophilins

A. R. Marks
Laboratory of Molecular Cardiology, Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, USA.

Immunophilins are members of a highly conserved family of proteins all of which are cis-trans peptidyl-prolyl isomerases. The prototypic members of the immunophilin family, cyclophilin A and FKPB12, were discovered on the basis of their ability to bind and mediate the immunosuppressive effects of the drugs cyclosporin, FK506, and rapamycin. However, the prolyl isomerase activity of these proteins is not involved in any of the immunosuppressive effects. Indeed, despite the fact that all members of the family are prolyl isomerases, the cellular role of this enzymatic function has not been clearly defined. In many cases, immunophilins are widely expressed and are present at high levels in some tissues. Moreover, while the number of proteins that belong to the immunophilin family continues to grow, the natural cellular functions of all but a few remain obscure. An example where immunophilins do appear to have a defined cellular role, in the absence of immunosuppressive ligands, is the modulation of intracellular calcium release channel function by FKBP12 and FKBP12.6. In this case, FKBPs are integral parts of three types of calcium release channel complexes, skeletal and cardiac ryanodine receptors and the inositol 1,4,5-trisphosphate receptor. In each case, FKBPs modulate channel function possibly by enhancing the cooperativity between subunits.

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