Monday, December 12, 2016

Loss of a doublecortin (DCX) domain protein causes structural defects in a tubulin-based organelle of Toxoplasma gondii and impairs host-cell invasion

2016 Dec 8. pii: mbc.E16-08-0587. [Epub ahead of print]

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 of the conoid fibers make canonical microtubules elsewhere in the same cell, suggesting that non-tubulin 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-alpha 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 re-introduction of a TgDCX coding sequence. The non-tubular 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.

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