Evidence that the Plasmodium falciparum Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries

Abstract

The malaria parasite is a massive burden in several parts of the world. Worryingly, the parasite has become resistant to several of the drugs commonly used to treat the disease, and at this time, there is no commercial vaccine. It is therefore critical to identify new targets for the development of antimalarials. To survive in the human body, the malaria parasite needs to invade red blood cells. For this, it uses a variety of effectors stored in organelles forming a structure called the apical complex. The mechanisms behind how the parasite generates the apical complex are poorly understood. In this study, we present evidence that a transmembrane protein called sortilin potentially acts as an escorter to transport proteins from the Golgi apparatus to the rhoptries, a component of the apical complex. Our study provides new insight into the biogenesis of a critical structure of the malaria parasite.

The malaria parasite Plasmodium falciparum Sortilin is essential for merozoite formation and apical complex biogenesis

“…Our recent finding that PfSortilin interacted with regions of RAMA sufficient for localisation to rhoptries provided support for Sortilin's role as a protein escorter to this organelle (Hallee et al, ). To provide more direct evidence, immunofluorescence assays (IFAs) were performed with antibodies to rhoptry proteins using the PfSortilin KD and control lines grown in the presence or absence of GlcN.…”

“…P. falciparum possesses a homologue of the Sortilin protein that localises to the Golgi apparatus (Hallee, Boddey, Cowman, & Richard, 2018;Koumandou et al, 2011;Krai et al, 2014), and we recently demonstrated that it interacted with regions of the glycosylphosphatidylinositol-anchored P. falciparum rhoptry-associated membrane antigen (RAMA) that were sufficient to drive a fluorescent reporter to the rhoptries which suggested that PfSortilin could act as an escorter for the trafficking of RAMA to these organelles (Hallee et al, 2018).…”

“…Our recent finding that PfSortilin interacted with regions of RAMA sufficient for localisation to rhoptries provided support for Sortilin's role as a protein escorter to this organelle (Hallee et al, 2018). To provide more direct evidence, immunofluorescence assays (IFAs)…”

Directing traffic: Chaperone‐mediated protein transport in malaria parasites

“…As for transport to Plasmodium rhoptries, no specific signals have yet been identified. However, certain regions within rhoptry proteins have been shown to be essential for localization (Ghoneim, Kaneko, Tsuboi, & Torii, 2007; Sherling et al, 2017) as well as interactions with other rhoptry proteins (Baldi et al, 2000; Hallée, Boddey, Cowman, & Richard, 2018; Morse, Webster, Kalanon, Langsley, & McFadden, 2016; Richard et al, 2009). The rhoprtry associated protein 1 (RAP1) was shown to contain a bipartite signal necessary and sufficient for trafficking to the rhoptries (Richard et al, 2009).…”

“…This possibility has not been explored further and the rhoptry targeting signals for other rhoptry proteins remain to be identified. More recent work, has suggested that certain members of the golgi‐endosomal protein trafficking pathway, such as homologs of sortilin or VPS10p, are repurposed for targeting proteins to rhoptries (Hallée et al, 2018). The Plasmodium sortilin homolog has been shown to interact with a rhoptry protein (Hallée et al, 2018), however, more work is required to show a direct involvement of the vacuolar protein sorting pathway in directing proteins to the rhoptries.…”