The ZIP Code of Vesicle Trafficking in Apicomplexa: SEC1/Munc18 and SNARE Proteins

Abstract

Apicomplexans are obligate intracellular parasites harboring three sets of unique secretory organelles termed micronemes, rhoptries, and dense granules that are dedicated to the establishment of infection in the host cell. Apicomplexans rely on the endolysosomal system to generate the secretory organelles and to ingest and digest host cell proteins. These parasites also possess a metabolically relevant secondary endosymbiotic organelle, the apicoplast, which relies on vesicular trafficking for correct incorporation of nuclear-encoded proteins into the organelle. Here, we demonstrate that the trafficking and destination of vesicles to the unique and specialized parasite compartments depend on SNARE proteins that interact with tethering factors. Specifically, all secreted proteins depend on the function of SLY1 at the Golgi. In addition to a critical role in trafficking of endocytosed host proteins, TgVps45 is implicated in the biogenesis of the inner membrane complex (alveoli) in both Toxoplasma gondii and Plasmodium falciparum, likely acting in a coordinated manner with Stx16 and Stx6. Finally, Stx12 localizes to the endosomal-like compartment and is involved in the trafficking of proteins to the apical secretory organelles rhoptries and micronemes as well as to the apicoplast. IMPORTANCE The phylum of Apicomplexa groups medically relevant parasites such as those responsible for malaria and toxoplasmosis. As members of the Alveolata superphylum, these protozoans possess specialized organelles in addition to those found in all members of the eukaryotic kingdom. Vesicular trafficking is the major route of communication between membranous organelles. Neither the molecular mechanism that allows communication between organelles nor the vesicular fusion events that underlie it are completely understood in Apicomplexa. Here, we assessed the function of SEC1/Munc18 and SNARE proteins to identify factors involved in the trafficking of vesicles between these various organelles. We show that SEC1/Munc18 in interaction with SNARE proteins allows targeting of vesicles to the inner membrane complex, prerhoptries, micronemes, apicoplast, and vacuolar compartment from the endoplasmic reticulum, Golgi apparatus, or endosomal-like compartment. These data provide an exciting look at the “ZIP code” of vesicular trafficking in apicomplexans, essential for precise organelle biogenesis, homeostasis, and inheritance.

Biogenesis and discharge of the rhoptries: Key organelles for entry and hijack of host cells by the Apicomplexa

“…The description of an interaction between the C‐terminal tail of SORTLR with AP1 and Vps proteins suggests a concerted role of these complexes in the trafficking of ROPs and MICs via a clathrin‐dependent process (Sloves et al., 2012). A recent study shows that the trafficking of vesicles to their specialized compartments depends on SNARE proteins (Bisio et al., 2020). Syntaxin (Stx)‐like SNARE protein 12 (Stx12) localizes to the ELC and is involved in the trafficking of proteins to rhoptries and micronemes as well as to the apicoplast.…”

“…Syntaxin (Stx)‐like SNARE protein 12 (Stx12) localizes to the ELC and is involved in the trafficking of proteins to rhoptries and micronemes as well as to the apicoplast. Disruption of Stx12 resulted in a decreased amount of mature microneme and rhoptry proteins along with a severe defect in invasion (Bisio et al., 2020).…”

Ferlins and TgDOC2 in Toxoplasma Microneme, Rhoptry and Dense Granule Secretion

“…Although Rab11A has been shown to be critical in constitutive secretion of dense granules, this is not a triggered event [ 102 ]. In addition, no Toxoplasma ’s SNARE proteins have been detected at the site of microneme and rhoptry secretion site in the very apical plasma membrane [ 103 ]. The most forward localizing SNARE in the secretory pathway identified is a syntaxin, TgStx12, which is critical in trafficking of proteins from ELC to the micronemes and rhoptries, but not for their secretion.…”

Identification of novel inner membrane complex and apical annuli proteins of the malaria parasitePlasmodium falciparum

“…The function of the Kelch13 compartment and cytostome-like structures in late schizont and merozoites remains to be elucidated. It could either represent a repurposing of these endocytosis-linked structures (Spielmann et al, 2020) for host cell invasion and the establishment of the parasite in a new host cell or serve an endocytosis-related function in schizonts, as it has been recently shown that schizonts still appear to endocytose host cell hemoglobin (Bisio et al, 2020).…”