A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii.
King, Thayer P
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Li, Z., King, T. P., Ayong, L., Asady, B., Cai, X., Rahman, T., Vella, S. A., et al. (2021). A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii.. Nature communications, 12 (1) https://doi.org/10.1038/s41467-021-25987-5
Two-pore channels (TPCs) are a ubiquitous family of cation channels that localize to acidic organelles in animals and plants to regulate numerous Ca<sup>2+</sup>-dependent events. Little is known about TPCs in unicellular organisms despite their ancient origins. Here, we characterize a TPC from Toxoplasma gondii, the causative agent of toxoplasmosis. TgTPC is a member of a novel clad of TPCs in Apicomplexa, distinct from previously identified TPCs and only present in coccidians. We show that TgTPC localizes not to acidic organelles but to the apicoplast, a non-photosynthetic plastid found in most apicomplexan parasites. Conditional silencing of TgTPC resulted in progressive loss of apicoplast integrity, severely affecting growth and the lytic cycle. Isolation of TPC null mutants revealed a selective role for TPCs in replication independent of apicoplast loss that required conserved residues within the pore-lining region. Using a genetically-encoded Ca<sup>2+</sup> indicator targeted to the apicoplast, we show that Ca<sup>2+</sup> signals deriving from the ER but not from the extracellular space are selectively transmitted to the lumen. Deletion of the TgTPC gene caused reduced apicoplast Ca<sup>2+</sup> uptake and membrane contact site formation between the apicoplast and the ER. Fundamental roles for TPCs in maintaining organelle integrity, inter-organelle communication and growth emerge.
NIAID NIH HHS (R01 AI128356, R01 AI096836, R01 AI060767, T32 AI060546)
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (T32AI060546, AI096836, AI128356)
NHLBI NIH HHS (T32 HL007895)
Biotechnology and Biological Sciences Research Council (BB/N01524X/1, BB/T015853/1)
RCUK | Biotechnology and Biological Sciences Research Council (BB/T015853/1, BB/N01524X/1)
U.S. Department of Health & Human Services | National Institutes of Health (R01AI060767, T32HL007895)
External DOI: https://doi.org/10.1038/s41467-021-25987-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330398
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/