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

Daniel N A Tagoe,Allison A Drozda,Eranthie Weerapana,Marc-Jan Gubbels,Julia A Falco,Tyler J Bechtel

doi:10.3390/life11030217

Abstract

The host cell invasion process of apicomplexan parasites like Toxoplasma gondii is facilitated by sequential exocytosis of the microneme, rhoptry and dense granule organelles. Exocytosis is facilitated by a double C2 domain (DOC2) protein family. This class of C2 domains is derived from an ancestral calcium (Ca2+) binding archetype, although this feature is optional in extant C2 domains. DOC2 domains provide combinatorial power to the C2 domain, which is further enhanced in ferlins that harbor 5–7 C2 domains. Ca2+ conditionally engages the C2 domain with lipids, membranes, and/or proteins to facilitating vesicular trafficking and membrane fusion. The widely conserved T. gondii ferlins 1 (FER1) and 2 (FER2) are responsible for microneme and rhoptry exocytosis, respectively, whereas an unconventional TgDOC2 is essential for microneme exocytosis. The general role of ferlins in endolysosmal pathways is consistent with the repurposed apicomplexan endosomal pathways in lineage specific secretory organelles. Ferlins can facilitate membrane fusion without SNAREs, again pertinent to the Apicomplexa. How temporal raises in Ca2+ combined with spatiotemporally available membrane lipids and post-translational modifications mesh to facilitate sequential exocytosis events is discussed. In addition, new data on cross-talk between secretion events together with the identification of a new microneme protein, MIC21, is presented.

Highlights

Published: 9 March 2021The opportunistic apicomplexan parasite Toxoplasma gondii causes significant disease in people with immature or compromised immune systems [1]
The secretory pathway that subsequently passes through the endoplasmic reticulum (ER) and Golgi apparatus mediates protein trafficking to the three secretory organelles
Pharmacological triggering of microneme release facilitated studies on the proteins discharged by the parasite from this organelle [50,51]

Summary

Introduction

The opportunistic apicomplexan parasite Toxoplasma gondii causes significant disease in people with immature or compromised immune systems [1]. Central to the pathogenesis of all apicomplexan parasites, including malaria causing Plasmodium falciparum, is the rapid serial completion of lytic replication rounds causing tissue damage and inflammation. Completion of the lytic cycle requires host cell invasion and egress, which are mediated by sequential exocytosis of, respectively, the apically located micronemes and rhoptries and the more scattered dense granules organelles [2,3] (Figure 1A,B). Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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