Toxoplasma IMC1 is a central component of the subpellicular network and plays critical roles in parasite morphology, replication, and infectivity
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Toxoplasma gondii and related apicomplexan parasites utilize a unique membrane and cytoskeletal organelle called the inner membrane complex (IMC) for maintaining cell shape, motility, host cell invasion, and replication. The cytoskeleton portion of the organelle is a network of filaments composed of proteins called alveolins, whose precise functions and organization are poorly understood. Here we describe the function of the founding member of the Toxoplasma alveolins, IMC1, which we show is expressed and loaded onto forming daughter buds with IMC4, but later than the other key alveolins IMC3, IMC6, and IMC10. Disruption of IMC1 results in severe morphological defects that impact the integrity of the parasite’s cytoskeleton and disrupt invasion, replication, and egress. Loss of IMC1 in a less virulent type II strain results in a dramatic loss of infectivity and complete failure to form a chronic infection. We then use deletion analyses to dissect functional regions of the protein which reveals a key subregion of the alveolin domain that is sufficient for IMC targeting and also required for function. We then show that IMC1 interacts directly with IMC4 and the loss of IMC1 results in mislocalization of IMC4 specifically in forming daughter buds. This study thus reveals the critical role that IMC1 plays in forming and maintaining the architecture of the filamentous network of the IMC.
Significance
Parasites in the phylum Apicomplexa maintain their intracellular lifestyle using specialized organelles that mediate the lytic cycle of host cell invasion, intracellular replication, and egress. One of these organelles is the inner membrane complex (IMC), which consists of membrane vesicles supported by a cytoskeletal meshwork formed from proteins called alveolins. This study focuses on the first identified alveolin IMC1 and determines its precise function via expression timing, gene knockout, deletion and mutagenesis, partner identification, and in vivo infection studies. We show that this protein is critical to the ultrastructure of the parasite which is important for every stage of its lytic cycle. We also identify key regions of the protein that are important for localization, function, and interaction with another key alveolin, IMC4.
