title: Loss of a doublecortin (DCX)-domain protein causes structural defects in a tubulin-based organelle of Toxoplasma gondii and impairs host-cell invasion.
abstract: The ∼6000 species in phylum Apicomplexa are single-celled obligate intracellular parasites. Their defining characteristic is the apical complex-membranous and cytoskeletal elements at the apical end of the cell that participate in host-cell invasion. The apical complex of Toxoplasma gondii and some other apicomplexans includes a cone-shaped assembly, the conoid, which in T. gondii comprises 14 spirally arranged fibers that are nontubular polymers of tubulin. The tubulin dimers of the conoid fibers make canonical microtubules elsewhere in the same cell, suggesting that nontubulin protein dictates their special arrangement in the conoid fibers. One candidate for this role is TgDCX, which has a doublecortin (DCX) domain and a TPPP/P25-α domain, both of which are known modulators of tubulin polymer structure. Loss of TgDCX radically disrupts the structure of the conoid, severely impairs host-cell invasion, and slows growth. Both the conoid structural defects and the impaired invasion of TgDCX-null parasites are corrected by reintroduction of a TgDCX coding sequence. The nontubular polymeric form of tubulin found in the conoid is not found in the host cell, suggesting that TgDCX may be an attractive target for new parasite-specific chemotherapeutic agents.
authors.affiliation: Nikon Instruments, Melville, NY 11747.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nagayasu
authors.affiliation: Nikon Instruments, Melville, NY 11747.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Hwang
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405.
authors.forename: John M
authors.initials: JM
authors.lastname: Murray
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405 kehu@indiana.edu.
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism; D014122:Toxoplasma / Q000235:genetics / Q000378:metabolism*; D014123:Toxoplasmosis / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D014404:Tubulin