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

Eiji Nagayasu, Yu Chen Hwang, Jun Liu, John M. Murray, Ke Hu, Fred Chang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)411-428
Number of pages18
JournalMolecular biology of the cell
Volume28
Issue number3
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Loss of a doublecortin (DCX)-domain protein causes structural defects in a tubulin-based organelle of Toxoplasma gondii and impairs host-cell invasion'. Together they form a unique fingerprint.

Cite this