Functional assays of the protein phosphatase calcineurin in the human parasite Schistosoma mansoni

• Applicant: Privatdozentin Dr. Mo Klinkert
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2001 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5301100

The proposed work is focussed on understanding the role of the calcium/calmodulin-dependent serine-threonine protein phosphatase calcineurin in the human parasite Schistosoma mansoni. We have previously cloned and expressed the calcineurin subunits, as a starting point in the detection of endogenous cellular proteins capable of associating with calcineurin. Amongst these, the immunophilin FK506 binding protein has been reproted to form a ternary complex with the calcium release channel, the inositol triphosphate receptor IP3R and calcineurin. Thus, a first logical step is to characterize FKBP at a molecular level. In a second line of research, we propose to conduct studies on the interaction of S. mansoni calcium ATPase SMA2 with calcineurin, coexpressing both parasite proteins in Saccharomyces cerevisiae. Previous experiments have demonstrated that SMA2 is negatively regulated by yeast calcineurin. We will attempt to investigate its regulation by the homologous calcineurin using yeast strains deleted in the corresponding genes. In this way, we may gain an insight into a role of calcineurin in calcium transport and may obtain results that will be relevant to understanding schistosome physiology and regulation of ion homeostasis.

• DFG Programme: Research Grants