The N-terminal signal peptide of the murine cyclophilin mCyP-S1 is required in vivo for ER localization.

Cyclophilins are a class of enzymes that are thought to be involved in protein folding by accelerating the isomerization of Xaa-Pro peptide bonds and that mediate the immunosuppressive effect of cyclosporin A. We described previously a murine cyclophilin, mCyP-S1, whose cDNA encoded a putative NH2-terminal signal sequence which was not present in the mature protein. Here we investigate the intracellular localization of mCyP-S1. We show by overexpression of the wild-type and an NH2-terminally truncated derivative that its signal sequence is necessary and functional in vivo for the translocation into the endoplasmic reticulum (ER). Immunocytochemistry and cell fractionations demonstrate the preferential localization of endogenous mCyP-S1 in the ER, or subcompartments thereof. In addition, the results indicate the presence of this cyclophilin in the nucleus.