Abstract
The inner membrane complex (IMC) of apicomplexan parasites contains a network of intermediate filament-like proteins. The 14 alveolin domain-containing IMC proteins in Toxoplasma gondii fall into different groups defined by their distinct spatiotemporal dynamics during the internal budding process of tachyzoites. Here, we analyzed representatives of different IMC protein groups across all stages of the Toxoplasma life cycle and during Sarcocystis neurona asexual development. We found that across asexually dividing Toxoplasma stages, IMC7 is present exclusively in the mother's cytoskeleton, whereas IMC1 and IMC3 are both present in mother and daughter cytoskeletons (IMC3 is strongly enriched in daughter buds). In developing macro- and microgametocytes, IMC1 and -3 are absent, whereas IMC7 is lost in early microgametocytes but retained in macrogametocytes until late in their development. We found no roles for IMC proteins during meiosis and sporoblast formation. However, we observed that IMC1 and IMC3, but not IMC7, are present in sporozoites. Although the spatiotemporal pattern of IMC15 and IMC3 suggests orthologous functions in Sarcocystis, IMC7 may have functionally diverged in Sarcocystis merozoites. To functionally characterize IMC proteins, we knocked out IMC7, -12, -14, and -15 in Toxoplasma. IMC14 and -15 appear to be involved in switching between endodyogeny and endopolygeny. In addition, IMC7, -12, and -14, which are all recruited to the cytoskeleton outside cytokinesis, are critical for the structural integrity of extracellular tachyzoites. Altogether, stage- and development-specific roles for IMC proteins can be discerned, suggesting different niches for each IMC protein across the entire life cycle. IMPORTANCE The inner membrane complex (IMC) is a defining feature of apicomplexan parasites key to both their motility and unique cell division. To provide further insights into the IMC, we analyzed the dynamics and functions of representative alveolin domain-containing IMC proteins across developmental stages. Our work shows universal but distinct roles for IMC1, -3, and -7 during Toxoplasma asexual division but more specialized functions for these proteins during gametogenesis. In addition, we find that IMC15 is involved in daughter formation in both Toxoplasma and Sarcocystis. IMC14 and IMC15 function in limiting the number of Toxoplasma offspring per division. Furthermore, IMC7, -12, and -14, which are recruited in the G1 cell cycle stage, are required for stress resistance of extracellular tachyzoites. Thus, although the roles of the different IMC proteins appear to overlap, stage- and development-specific behaviors indicate that their functions are uniquely tailored to each life stage requirement.
Highlights
The inner membrane complex (IMC) of apicomplexan parasites contains a network of intermediate filament-like proteins
The profile observed in bradyzoites does reflect the profile in tachyzoites. This suggests that IMC proteins will behave the same in tachyzoites and bradyzoites, which matches with the similar endodyogeny division strategy followed by these two stages [21]
The absence of IMC12 appeared to increase the parasites’ resistance to osmotic stress conditions (Fig. 10D). These results indicate that IMC7, -12, and -14 have distinct and even opposing roles in the maintenance of extracellular parasite rigidity. Apicomplexan parasites adapt their division modes between different hosts and tissues, and we hypothesized that IMC proteins play differential roles in these division modes
Summary
The inner membrane complex (IMC) of apicomplexan parasites contains a network of intermediate filament-like proteins. The 14 alveolin domain-containing IMC proteins in Toxoplasma gondii fall into different groups defined by their distinct spatiotemporal dynamics during the internal budding process of tachyzoites. The Toxoplasma tachyzoite divides by endodyogeny, an internal budding process forming two daughter parasites per division round [4]. Infection of a cat leads to several rounds of merogony in the epithelial cells of the small intestine At this stage, the parasite divides by endopolygeny, which involves repeated rounds of S phase and nuclear division, followed by the formation of multiple daughters by a final mitosis round linked to internal budding. Cell division of the nonsexual stages is driven by assembly of the cortical cytoskeleton composed of flattened alveolar sacs undergirded by an intermediate filament network and microtubules [8] This cortical membrane complex is called the inner membrane complex (IMC). IMC5, -8, -9, and -13 transition to the basal end msphere.asm.org 2
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.