The Conoid Associated Motor MyoH Is Indispensable for Toxoplasma gondii Entry and Exit from Host Cells.

Arnault Graindorge,Damien Jacot,Dominique Soldati-Favre,Julien Salamun,Jean Baptiste Marq,Karine Frénal,Marc-Jan Gubbels

doi:10.1371/journal.ppat.1005388

Abstract

Many members of the phylum of Apicomplexa have adopted an obligate intracellular life style and critically depend on active invasion and egress from the infected cells to complete their lytic cycle. Toxoplasma gondii belongs to the coccidian subgroup of the Apicomplexa, and as such, the invasive tachyzoite contains an organelle termed the conoid at its extreme apex. This motile organelle consists of a unique polymer of tubulin fibres and protrudes in both gliding and invading parasites. The class XIV myosin A, which is conserved across the Apicomplexa phylum, is known to critically contribute to motility, invasion and egress from infected cells. The MyoA-glideosome is anchored to the inner membrane complex (IMC) and is assumed to translocate the components of the circular junction secreted by the micronemes and rhoptries, to the rear of the parasite. Here we comprehensively characterise the class XIV myosin H (MyoH) and its associated light chains. We show that the 3 alpha-tubulin suppressor domains, located in MyoH tail, are necessary to anchor this motor to the conoid. Despite the presence of an intact MyoA-glideosome, conditional disruption of TgMyoH severely compromises parasite motility, invasion and egress from infected cells. We demonstrate that MyoH is necessary for the translocation of the circular junction from the tip of the parasite, where secretory organelles exocytosis occurs, to the apical position where the IMC starts. This study attributes for the first time a direct function of the conoid in motility and invasion, and establishes the indispensable role of MyoH in initiating the first step of motility along this unique organelle, which is subsequently relayed by MyoA to enact effective gliding and invasion.

Highlights

The phylum of Apicomplexa includes numerous human and animal pathogens that have adopted an obligate intracellular life style and critically depend on active invasion and egress from the infected cells to ensure survival and propagation
Toxoplasma gondii exhibits a helical form of gliding motility and as member of the coccidian-subgroup of Apicomplexa possesses an apical organelle called the conoid, which protrudes during invasion and egress and consists in helically organized polymer of tubulin fibers
Both host cell entry and exit are driven by gliding motility, a process involving conserved machinery termed the glideosome, located in the space between the inner membrane complex (IMC) and the parasite plasma membrane where adhesins are translocated from the apical to the posterior pole [1]

Summary

Introduction

The phylum of Apicomplexa includes numerous human and animal pathogens that have adopted an obligate intracellular life style and critically depend on active invasion and egress from the infected cells to ensure survival and propagation. Host cell entry is initiated by the attachment and reorientation of the polarized parasites, such that the apical secretory organelles (micronemes and rhoptries) sequentially discharge their contents at the point of contact with the host cell plasma membrane. Adhesins and other proteins are secreted apically by the micronemes and among them, AMA1 forms a complex with a set of rhoptry neck proteins (RONs) to establish a tight apposition between the parasite and the host cell membrane [2]. This attachment zone forms a ring-like structure called the moving junction [3] and through which the parasite enters the host cell [4].

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