Two palmitoyl acyltransferases involved sequentially in the biogenesis of the inner membrane complex of Toxoplasma gondii. (31st May 2020) - Dogga, Sunil Kumar
Abstract: The phylum Apicomplexa includes a number of significant human pathogens like Toxoplasma gondii and Plasmodium species. These obligate intracellular parasites possess a membranous structure, the inner membrane complex (IMC), composed of flattened vesicles apposed to the plasma membrane. Numerous proteins associated with the IMC are anchored via a lipid post‐translational modification termed palmitoylation. This acylation is catalysed by multi‐membrane spanning protein S‐acyl‐transferases (PATs) containing a catalytic Asp‐His‐His‐Cys (DHHC) motif, commonly referred to as DHHCs. Contrasting the redundancy observed in other organisms, several PATs are essential for T. gondii tachyzoite survival; 2 of them, TgDHHC2 and TgDHHC14 being IMC‐resident. Disruption of either of these TgDHHCs results in a rapid collapse of the IMC in the developing daughter cells leading to dramatic morphological defects of the parasites while the impact on the other organelles is limited to their localisation but not to their biogenesis. The acyl‐transferase activity of TgDHHC2 and TgDHHC14 is involved sequentially in the formation of the sub‐compartments of the IMC. Investigation of proteins known to be palmitoylated and localised to these sub‐compartments identified TgISP1/3 as well as TgIAP1/2 to lose their membrane association revealing them as likely substrates of TgDHHC2, while these proteins are not impacted by TgDHHC14 depletion. Abstract : Two palmitoyl acyl‐transferases (PATs) of Toxoplasma gondii have distinct localization within the inner membrane complex (IMC), being embedded within the full structure (TgDHHC2) or restricted to the transverse sutures (TgDHHC14). Both enzymes are individually essential for the survival of the tachyzoite, their acyl‐transferase activity being required sequentially for the biogenesis of the IMC sub‐compartments. They have distinct substrates based on their localization; TgISP1 and TgISP3 being likely substrates of TgDHHC2 while substrates of TgDHHC14 await to be identified.