The Conoid Associated Motor MyoH Is Indispensable for Toxoplasma gondii Entry and Exit from Host Cells.
The Conoid Associated Motor MyoH Is Indispensable for Toxoplasma gondii Entry and Exit from Host Cells.
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DOI：
10.1371/journal.ppat.1005388
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发表时间：
2016-01
期刊：
影响因子：
6.7
通讯作者：
Soldati-Favre D
中科院分区：
文献类型：
--
作者：
Graindorge A;Frénal K;Jacot D;Salamun J;Marq JB;Soldati-Favre D
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. The Apicomplexa phylum groups important pathogens that infect humans and animals. Host cell invasion and egress from infected cells are key events in the lytic cycle of these obligate intracellular parasites. Host cell entry is powered by gliding motility and initiated by the discharge of apical secretory organelles at the site of contact with the host cell. Anchored to the parasite pellicle, the glideosome composed of myosin A and the gliding associated proteins is the molecular machine which translocates the secreted adhesins from the apical to the posterior pole of the parasite and hence propels the parasite into the host cell. 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. We have deciphered here the function of a novel myosin associated to the microtubules composing the conoid. Myosin H is essential and prerequisite for motility, invasion and egress from infected cells. This unusual motor links actin- and tubulin-based cytoskeletons and uncovers a direct role of the conoid in motility and invasion.
