Loss of a doublecortin (DCX) domain containing 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 non-tubular polymers of tubulin. The tubulin dimers used for the conoid fibers make canonical microtubules elsewhere in the same cell, suggesting that their special arrangement in the conoid fibers is dictated by non-tubulin proteins. One candidate for this role is TgDCX, which has a doublecortin (DCX) domain and a TPPP/P25-alpha domain, known modulators of tubulin polymer structure. Loss of TgDCX radically disrupts the structure of the conoid, severely impairs host cell invasion, and slows growth. The defects of TgDCX-null parasites are corrected by re-introduction of a TgDCX coding sequence.