Perforin-Like Proteins of Apicomplexan Parasites.

Juliane Sassmannshausen,Sandra Bennink,Gabriele Pradel

doi:10.3389/fcimb.2020.578883

Abstract

Perforins are secreted proteins of eukaryotes, which possess a membrane attack complex/perforin (MACPF) domain enabling them to form pores in the membranes of target cells. In higher eukaryotes, they are assigned to immune defense mechanisms required to kill invading microbes or infected cells. Perforin-like proteins (PLPs) are also found in apicomplexan parasites. Here they play diverse roles during lifecycle progression of the intracellularly replicating protozoans. The apicomplexan PLPs are best studied in Plasmodium and Toxoplasma, the causative agents of malaria and toxoplasmosis, respectively. The PLPs are expressed in the different lifecycle stages of the pathogens and can target and lyse a variety of cell membranes of the invertebrate and mammalian hosts. The PLPs thereby either function in host cell destruction during exit or in overcoming epithelial barriers during tissue passage. In this review, we summarize the various PLPs known for apicomplexan parasites and highlight their roles in Plasmodium and Toxoplasma lifecycle progression.

Highlights

Members of the pore-forming Membrane Attack Complex/Perforin (MACPF) superfamily are highly conserved in both prokaryotes and eukaryotes, and are mainly used for immune defense or virulence
We here review the role of apicomplexan perforin-like proteins (PLPs) (ApiPLPs) during lifecycle progression, with special focus on the processes of cell traversal and host cell egress
Like for T. gondii, egress of Plasmodium from the host cell is mediated by a signaling cascade that involves the sequential activation of a PKG by cGMP and of CDPKs by increased cytosolic calcium and this process results in the discharge of vesicles important for red blood cell (RBC) lysis

Summary

Introduction

Members of the pore-forming Membrane Attack Complex/Perforin (MACPF) superfamily are highly conserved in both prokaryotes and eukaryotes, and are mainly used for immune defense or virulence. We here review the role of apicomplexan PLPs (ApiPLPs) during lifecycle progression, with special focus on the processes of cell traversal and host cell egress.

Results

Conclusion