RON 12, a novel  P lasmodium  ‐specific rhoptry neck protein important for parasite proliferation

Ellen Knuepfer,Ursula Straschil,Oniz Suleyman,Anton R Dluzewski,Anthony A Holder,Rita Tewari,Munira Grainger,Solabomi A Ogun,Aisling H O'Keeffe,Judith L Green

doi:10.1111/cmi.12181

RON 12, a novel P lasmodium ‐specific rhoptry neck protein important for parasite proliferation

Ellen Knuepfer, Ursula Straschil + Show 8 more

Open Access

https://doi.org/10.1111/cmi.12181

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Abstract

Apicomplexan parasites invade host cells by a conserved mechanism: parasite proteins are secreted from apical organelles, anchored in the host cell plasma membrane, and then interact with integral membrane proteins on the zoite surface to form the moving junction (MJ). The junction moves from the anterior to the posterior of the parasite resulting in parasite internalization into the host cell within a parasitophorous vacuole (PV). Conserved as well as coccidia-unique rhoptry neck proteins (RONs) have been described, some of which associate with the MJ. Here we report a novel RON, which we call RON12. RON12 is found only in Plasmodium and is highly conserved across the genus. RON12 lacks a membrane anchor and is a major soluble component of the nascent PV. The bulk of RON12 secretion happens late during invasion (after parasite internalization) allowing accumulation in the fully formed PV with a small proportion of RON12 also apparent occasionally in structures resembling the MJ. RON12, unlike most other RONs is not essential, but deletion of the gene does affect parasite proliferation. The data suggest that although the overall mechanism of invasion by Apicomplexanparasites is conserved, additional components depending on the parasite–host cell combination are required.

Highlights

The Apicomplexa is a protozoan phylum containing thousands of mostly obligate intracellular parasites
Apicomplexan parasites invade host cells by a conserved mechanism: parasite proteins are secreted from apical organelles, anchored in the host cell plasma membrane, and interact with integral membrane proteins on the zoite surface to form the moving junction (MJ)
The junction moves from the anterior to the posterior of the parasite resulting in parasite internalization into the host cell within a parasitophorous vacuole (PV)

Summary

Introduction

The Apicomplexa is a protozoan phylum containing thousands of mostly obligate intracellular parasites. It is believed that parasites attach to host cells using low-affinity interactions between parasite plasma membrane-anchored surface proteins and host cell receptors. This initial attachment has been visualized in the case of Plasmodium and Babesia merozoites invading erythrocytes, as dramatic movement of the zoite over the host cell resulting in frequent and extensive deformation of the erythrocyte (Gilson and Crabb, 2009; Asada et al, 2012). The newly invaded parasite resides in the host cell within its own niche of the PV where it feeds and replicates before egress and another cycle of host cell invasion

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