Lysine methylation found to control movement in single-celled parasites

LMU researchers identify a molecular mechanism that enables single-celled parasites to switch on the machinery they need to move and invade host cells.

Parasites such as Toxoplasma gondii and the malaria parasite Plasmodium falciparum depend on rapid, precisely controlled movement to complete their life cycles. To start moving, they must assemble actin filaments at their front end and connect them to the molecular machinery that generates force. How these events are coordinated has remained unclear.

A team led by Dr. Elena Jimenez-Ruiz at LMU's Faculty of Veterinary Medicine has now shown that in T. gondii, two lysine methyltransferases become active sequentially at the pointed end of the parasite.

The newly characterized enzyme PCKMT positions the actin nucleator Formin-1 at the parasite tip, allowing local actin assembly and protrusion of the conoid, a specialized structure involved in invasion. A second methyltransferase, AKMT, then participates in the downstream reorganization that couples the actin network to force transmission.

What surprised us is that methylation is not acting here in the nucleus, where it is best known, but directly at the parasite's motility machinery. These two enzymes appear to organize the transition from a parasite that is prepared to move to one that can actually generate force."

Dr. Elena Jimenez-Ruiz at LMU's Faculty of Veterinary Medicine

After the scientists removed PCKMT, Formin-1 failed to localize correctly, actin assembly did not initiate, and the parasites could no longer efficiently move, exit host cells, or invade new ones. The researchers also found that the related enzyme PfSET9 localizes to the apical end of P. falciparum and that its depletion strongly impairs invasion of red blood cells, suggesting that this regulatory principle may extend across so-called
apicomplexan parasites.

The findings reveal lysine methylation as an unexpected regulatory layer connecting signaling, cytoskeletal activation, and mechanical force. Because these methyltransferases are specific to apicomplexan parasites, they could provide promising starting points for drug development: compounds that block their activity might disrupt parasite movement and invasion without targeting equivalent enzymes in human cells.