A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii


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Authors
King, Thayer P. 
Ayong, Lawrence 
Asady, Beejan 
Abstract

Abstract: Two-pore channels (TPCs) are a ubiquitous family of cation channels that localize to acidic organelles in animals and plants to regulate numerous Ca2+-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 Ca2+ indicator targeted to the apicoplast, we show that Ca2+ 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 Ca2+ 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.

Description

Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)


Funder: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)

Keywords
Article, /631/80/86/1999, /631/80/642, /631/326/417/2552, /96/35, /13/31, /13/1, /13/106, /14/28, /14/19, /14/35, /14/34, /14/63, /38/1, /45/23, /45/77, /96/34, /147/143, article
Journal Title
Nature Communications
Conference Name
Journal ISSN
2041-1723
Volume Title
12
Publisher
Nature Publishing Group UK
Sponsorship
U.S. Department of Health & Human Services | National Institutes of Health (NIH) (T32HL007895, R01AI060767)
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (T32AI060546, AI128356, AI096836)
RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (BB/N01524X/1, BB/T015853/1)