1. A conserved complex of microneme proteins mediates rhoptry discharge in Toxoplasma.
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Valleau, Dylan, Sidik, Saima M, Godoy, Luiz C, Acevedo‐Sánchez, Yamilex, Pasaje, Charisse Flerida A, Huynh, My‐Hang, Carruthers, Vern B, Niles, Jacquin C, and Lourido, Sebastian
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APICOMPLEXA , *PARASITE life cycles , *TOXOPLASMA , *TOXOPLASMA gondii , *PROTEINS , *CELL membranes - Abstract
Apicomplexan parasites discharge specialized organelles called rhoptries upon host cell contact to mediate invasion. The events that drive rhoptry discharge are poorly understood, yet essential to sustain the apicomplexan parasitic life cycle. Rhoptry discharge appears to depend on proteins secreted from another set of organelles called micronemes, which vary in function from allowing host cell binding to facilitation of gliding motility. Here we examine the function of the microneme protein CLAMP, which we previously found to be necessary for Toxoplasma gondii host cell invasion, and demonstrate its essential role in rhoptry discharge. CLAMP forms a distinct complex with two other microneme proteins, the invasion‐associated SPATR, and a previously uncharacterized protein we name CLAMP‐linked invasion protein (CLIP). CLAMP deficiency does not impact parasite adhesion or microneme protein secretion; however, knockdown of any member of the CLAMP complex affects rhoptry discharge. Phylogenetic analysis suggests orthologs of the essential complex components, CLAMP and CLIP, are ubiquitous across apicomplexans. SPATR appears to act as an accessory factor in Toxoplasma, but despite incomplete conservation is also essential for invasion during Plasmodium falciparum blood stages. Together, our results reveal a new protein complex that mediates rhoptry discharge following host‐cell contact. Synopsis: Apicomplexan parasites discharge rhoptries and invade host cells through secretion of surface‐exposed microneme proteins. Here, a complex of three apicomplexan‐specific microneme proteins, CLAMP, CLIP, and SPATR, is shown to be essential for engagement of the rhoptry secretion machinery in the parasites Toxoplasma gondii and Plasmodium falciparum. A microneme protein complex composed of CLAMP, CLIP, and SPATR is required for rhoptry secretion and invasion in T. gondii and P. falciparum.The essential components of the complex, CLAMP and CLIP, are conserved among apicomplexan parasites.Development of a quantitative mass‐spectrometry method enables global measurement of changes in the Ca2+‐dependent excretory‐secretory antigen secretome of T. gondii.Removal of the cytosolic C‐terminal proline‐rich domain of CLAMP blocks rhoptry secretion, reflecting a likely role in signal transduction across the parasite plasma membrane. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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