ABOVE: Toxoplasma gondii relies on the timely arrival of proteins for successful replication via budding. ©iStock, Dr_Microbe
Toxoplasma gondii (T. gondii) infects one in three people at some point during their lifetimes. Immunocompromised and pregnant populations are particularly at risk of side effects or death.1 The parasite replicates, reminiscent of a scene from Alien, through internal budding using an organelle called the inner membrane complex (IMC) to form daughter buds within a mother cell. The IMC scaffold plays a crucial role in replication and recruits most proteins after daughter bud initiation.2 Identifying early arrival proteins in the IMC complex is crucial for guiding the development of antiparasite therapy.
It’s a new chapter in the budding literature of Toxoplasma.
–Marc-Jan Gubbels, Boston College
While scientists know many daughter IMC proteins, most are recruited post bud initiation, leaving the early recruited IMC proteins less understood. This motivated Peter Bradley, a cell biologist at the University of California, Los Angeles, to pinpoint early recruited IMC proteins as potential targets for curbing parasite-related diseases. In a paper published in PLOS Pathogens, Bradley and his team identified a novel IMC protein essential for constructing early daughter buds.3
“The protein scaffold for making daughter buds has a surprising number of redundancies,” said Bradley. “Only some of these earliest daughter proteins are essential.”
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The team conducted a genomic screen and homed in on one protein, IMC43, due to its genetic similarity to IMC32, an early stage protein that Bradley’s team previously identified as essential for replication.4 By staining, they noted that IMC43 arrived at the earliest stage of budding.
Not only was IMC43 punctual, but its absence also contributed to the collapse of the IMC scaffold, resulting in severe morphological defects, and decreasing the viability of the parasite. By looking at IMC43 and IMC32 together, “We figured they’d likely partner with one another,” said Bradley.
Binding assays revealed that the IMC43-IMC32 duo was indeed necessary for daughter bud formation. Another protein the team identified, IMC44, was dispensable in this binding interaction and underscored the importance of IMC43-IMC32’s necessity in replication, structural integrity, and parasite survival.
“This study demonstrates substantial insights into the protein relationships [within the core assembly complex],” said Marc-Jan Gubbels, a cell biologist at Boston College who was not involved in the study. “It’s a new chapter in the budding literature of Toxoplasma.”
Bradley was surprised that the IMC proteins of this replication process were not conserved. The findings suggested that IMC43, unlike IMC32, was specific to T. gondii and no other apicomplexan parasites (for example, Plasmodium).
Intrigued by the differences in core IMC proteins, Bradley plans to identify other important proteins and understand the regulation of these protein-protein interactions to develop vital drugs and vaccines for diseases caused by these parasites.
References
- Pappas G, et al. Toxoplasmosis snapshots: Global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int J Parasitol. 2009;39(12):1385-1394.
- Anderson-White BR, et al. A family of intermediate filament-like proteins is sequentially assembled into the cytoskeleton of Toxoplasma gondii. Cell Microbiol. 2011;13(1):18-31.
- Pasquarelli RR, et al. Identification of IMC43, a novel IMC protein that collaborates with IMC32 to form an essential daughter bud assembly complex in Toxoplasma gondii. PLoS Pathog. 2023;19(10):e1011707.
- Back PS, et al. IMC29 Plays an Important Role in Toxoplasma Endodyogeny and Reveals New Components of the Daughter-Enriched IMC Proteome. mBio. 2023;14(1):e0304222.
