Calcium transfer from the ER to other organelles for optimal signaling in Toxoplasma gondii.

Ca(2+) signaling in cells begins with the opening of Ca(2+) channels in either the plasma membrane (PM) or the endoplasmic reticulum (ER) and results in a dramatic increase in the physiologically low (<100 nM) cytosolic Ca(2+) level. The temporal and spatial Ca(2+) levels are well regulated to enable precise and specific activation of critical biological processes. Ca(2+) signaling regulates pathogenic features of apicomplexan parasites like Toxoplasma gondii which infects approximately one-third of the world's population. T. gondii relies on Ca(2+) signals to stimulate traits of its infection cycle and several Ca(2+) signaling elements play essential roles in its parasitic cycle. Active egress, an essential step for the infection cycle of T. gondii is preceded by a large increase in cytosolic Ca(2+) most likely by release from intracellular stores. Intracellular parasites take up Ca(2+) from the host cell during host Ca(2+) signaling events to replenish intracellular stores. In this work, we investigated the mechanism by which intracellular stores are replenished with Ca(2+) and demonstrated a central role for the SERCA-Ca(2+)-ATPase in keeping not only the ER filled with Ca(2+) but also other stores. We show mitochondrial Ca(2+) uptake, by transfer of Ca(2+) from the ER likely through membrane contact sites. We propose a central role for the ER in sequestering and redistributing calcium to other intracellular organelles following influx at the PM.