Ross Waller Profile picture
Jun 3 12 tweets 6 min read
Very pleased to present our recent study of #endocytosis in #apicomplexans that draws on #K13 and drug-resistance in #malaria to learn of a highly unusual endocytic machinery in #Toxoplasma with a deep evolutionary origin.…
Using the #Plasmodium #artemisinin-resistance genes as initial leads, some proximity proteomics, and a good deal of super-res microscopy, a comprehensive molecular model of endocytic pits integrated into the cell’s complex (IMC) pellicle was achieved.
Remarkably, this superstructure is highly stable with the typically ephemeral proteins rigidly anchored at this site. Even more unusual, the complex is preassembled in daughter cells before the plasma membrane is even recruited. (and yes, Toxo daughter cells ARE gorgeous!)
These data show that the Plasmodium cytostome, the instrument for haemoglobin feeding, is compositionally conserved in Toxoplasma. Furthermore, Simon Gras's lab developed a new endocytosis assay using Halo tags that enabled endocytosis to be monitored at this site.
But what is endocytosis used for by Toxoplasma? Suppression led to parasite death, however not via starvation. Rather, the parasites lost control of their plasma membrane. Chaotic membranes ballooned between parasites, and their typical tidy organisation and integrity was lost.
So, plasma membrane homeostasis — taking back up what is let out during secretory processes — is a key function of endocytosis in these parasites.
Back to the core machinery, there are several modifications apparent. K13 is a conspicuous signature of this structure, but a new protein derived from, and in addition to, AP-2alpha (we call KAE) has expanded the composition of this canonical #adaptor function.
These novel molecular features (and others) show a mirrored pattern of deep evolution in the common ancestors of apicomplexans, dinoflagellates, and their allies. Perhaps this isn’t surprising as a ‘micropore’ putative endocytic pit has been described in all of them.
But why would endocytic machinery and its behaviours be overhauled like this, and ruin all those otherwise perfectly good molecular cell biology textbooks?
Our data point to early adaptations for endocytosis in this important lineage where a common complex cell pellicle limits ready access of the dynamic endocytic machinery to the plasma membrane. This system is apparently shared with dinoflagellates, chrompodellids and perkinsids.
A great team effort spanning labs, countries, and continents: Ludek Koreny, @brandonms01, Christen Klinger, Konstantin Barylyuk, @SWButterworth, Jennifer Hirst, @YRiveraCu, Nathan Zaccai, Victoria Holzer, Andreas Klingl, @DacksJoel, @VernCarruthers, Margaret Robinson, Simon Gras
PS, at the start of this project I had some great discussions with David Warhurst about K13. I’m very sorry that he didn’t see its fruition.

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