Calcium transfer from the ER to other organelles for optimal signaling inToxoplasma gondii

Ca²⁺signaling in cells begins with the opening of Ca²⁺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 Ca²⁺level. The temporal and spatial Ca²⁺levels are well regulated to enable precise and specific activation of critical biological processes. Ca²⁺signaling regulates pathogenic features of apicomplexan parasites likeToxoplasma gondiiwhich infects approximately one-third of the world’s population.T. gondiirelies on Ca²⁺signals to stimulate traits of its infection cycle and several Ca²⁺signaling elements play essential roles in its parasitic cycle. Active egress, an essential step for the infection cycle ofT. gondiiis preceded by a large increase in cytosolic Ca²⁺most likely by release from intracellular stores. Intracellular parasites take up Ca²⁺from the host cell during host Ca²⁺signaling events to replenish intracellular stores. In this work, we investigated the mechanism by which intracellular stores are replenished with Ca²⁺and demonstrated a central role for the SERCA-Ca²⁺-ATPase in keeping not only the ER filled with Ca²⁺but also other stores. We show mitochondrial Ca²⁺uptake, by transfer of Ca²⁺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.