SCHISTOSOMA-MANSONI CA2-ATPASE SMA2 RESTORES VIABILITY TO YEAST CA2+-ATPASE-DEFICIENT STRAINS AND FUNCTIONS IN CALCINEURIN-MEDIATED CA2+ TOLERANCE()

The sarco(endo)plasmic reticulum of animal cells contains an ATP-power ed Ca2+ pump that belongs to the P-type family of membrane-bound catio n-translocating enzymes. In Schistosoma mansoni, the sarco(endo)plasmi c reticulum Ca2+-ATPase (SERCA) is encoded by the SMA1 and SMA2 genes. A full-length SMA2 cDNA clone was isolated, sequenced, and expressed into a yeast Ca2+-ATPase-deficient strain requiring plasmid-borne rabb it SERCA1a for viability. The S. mansoni Ca2+-ATPase supports growth o f mutant cells lacking SERCA1a, indicating functional expression in ye ast and a role in calcium sequestration. Subcellular fractionation sho wed that the SMA2 ATPase is localized in yeast internal membranes. SMA 2 expression was found to be associated with thapsigargin-sensitive, C a2+-dependent ATPase activity. The activity increased 2-fold upon calc ineurin inactivation, which correlates with in vivo stimulated contrib ution of SMA2 in calcium tolerance. These results suggest that calcine urin controls calcium homeostasis by inhibiting Ca2+-ATPase activity i n an internal compartment.