Cytological and biochemical evidence for a gonad-preferential interplay of SmFKBP12 and SmTbetaR-I in Schistosoma mansoni.

In eukaryotes, FK506-binding proteins with a molecular weight of 12 kDa (FKBP12s) influence a variety of signal transduction pathways that regulate cell division, differentiation, and ion homeostasis. Amongst these, TGFbeta signaling and calcineurin (CN) phosphatase activity is modulated by FKBP12 via binding to TGFbeta-family type I receptors (TbetaR-Is) or to the CN subunit A, respectively. In this work, we demonstrate the tissue-specific expression of the Schistosoma mansoni FKBP12 homologue (SmFKBP12) in the gonads of female parasites as well as in the tegument of both genders. Components of the TGFbeta pathway have been characterized in schistosomes and their roles in mediating host-parasite or male-female interactions proposed. We show that a schistosome TGFbeta-family type I receptor (SmTbetaR-I, SmRK-1) is expressed in the female gonads, suggesting that SmFKBP12 may regulate its activity in this tissue. This hypothesis is supported by yeast two-hybrid analyses showing a direct binding of SmFKBP12 and SmTbetaR-I, which was specifically inhibited by the drug FK506. Our data provide the first evidence for the activity of a transmembrane receptor in the vitellarium of schistosome females and indicate that FKBP12-meditated regulation of the TGFbeta pathway is evolutionarily conserved in a primitive metazoan such as Schistosoma. Furthermore, we show that the schistosome CN (SmCN) is not expressed in the female gonads, but co-localizes with SmFKBP12 only in the tegument. From these data we conclude an SmFKBP12/SmTbetaR-I, but not an SmCN/SmFKBP12 interplay in the female gonads.