Doctor Elena Jimenez Ruiz

Exploring Post-Translational Methylation Dynamics in Apicomplexan Parasites for Insights into Cytoskeletal Regulation

    The addition of methyl groups to proteins plays a crucial role in regulating protein-protein interactions. Recently, the methylation of cytoskeletal proteins, such as actin and tubulin, has gained prominence due to its role in locally and contextually regulating their dynamics. In apicomplexans, the methylated residues in tubulin and actin are conserved, but their functions remain largely unknown.

    We recently identified a SET methyltransferase (PCKMT) localized to the conoid, a vital apical structure crucial for invasion and motility. Intriguingly, PCKMT plays a pivotal role in recruiting the actin nucleator formin 1 (FRM1). Additionally, an independent apical methyltransferase (AKMT) has been shown to be essential for recruiting the gliding-associated connector (GAC) to the conoid. Both FRM1 and GAC are critical factors involved in initiating motility and facilitating force transmission in Toxoplasma gondii.

    We speculate that AKMT and PCKMT have distinct and crucial roles in methylating the parasite's cytoskeleton, ultimately leading to the recruitment of other factors like GAC and FRM1. Numerous other factors are localized in this structure and seem to play vital roles in initiating and progressing motility. Recently, we identified a key conoidal protein, conoid gliding protein (CGP), in a phenotypic screen (Li et al., 2022. Nat Microbiol). CGP is a structural component of the gliding initiation complex (GIC), which also includes PCKMT and FRM1.

Our research focuses on:
-Identifying and characterizing factors involved in motility and egress.
-Understanding the role of methylation in regulating the dynamics of cytoskeletal proteins.
-Identifying apicomplexan-specific methyltransferases crucial for parasite survival.