Calcium tunneling through the ER and transfer to other organelles for optimal signaling inToxoplasma gondii

Abstract

ABSTRACTCa2+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 to keep not only the ER filled with Ca2+but also acidic stores. We also show mitochondrial Ca2+uptake, by transfer of Ca2+from the ER most likely through membrane contact sites. We propose a central role for the ER in tunneling of calcium from the extracellular milieu through the ER to other organelles.HIGHLIGHTSTheT. gondiiER efficiently takes up Ca2+that enters the cytosol from the extracellular milieu.Filling of acidic stores inT. gondiiappears to be dependent on the filling of the ERThe mitochondrion ofT. gondiihas no direct access to extracellular calcium but is able to take up Ca2+by transfer from the ER and/or acidic stores