ICMAP1

TgICMAP1 is a microtubule-binding protein of Toxoplasma gondii that directly associates with and stabilizes microtubules and localizes specifically to the intra-conoid microtubules (ICMTs) rather than other tubulin-containing structures of the parasite (PMID:19823689). It defines a family of ICMT-associated proteins: the related ICMAP2 and ICMAP3 scaffold the ICMTs to support iterative rhoptry docking and discharge, a process essential for host-cell invasion and virulence (PMID:38191574). Depletion of ICMAP2 dissociates the ICMTs, detaches them from the conoid, and disperses microtubule-associated vesicles and rhoptries, while the two ICMAP3 isoforms respectively control ICMT length and docking of rhoptries at the apical vesicle (PMID:38191574). Beyond microtubule binding and stabilization by ICMAP1 (PMID:19823689) and the scaffolding role of its relatives (PMID:38191574), no further mechanistic detail has been characterized in the available corpus.

1. 2009 High

   It was unknown whether ICMAP1 was a bona fide microtubule-associated protein and which of the parasite's tubulin structures it served; direct binding assays and localization established it as a microtubule-stabilizing protein specific to the intra-conoid microtubules.

   Evidence In vitro microtubule binding assay, ectopic expression in mammalian cells, and fluorescence localization in T. gondii

   PMID:19823689

   Open questions at the time

   • No loss-of-function phenotype for ICMAP1 itself established
   • The functional consequence of ICMT stabilization for parasite biology not addressed
   • No structural basis of the microtubule interaction defined
2. 2024 High

   It was unknown what cellular function the intra-conoid microtubules serve; depletion of the related ICMAP2 and ICMAP3 showed the ICMTs scaffold iterative rhoptry docking and discharge required for invasion and virulence.

   Evidence Conditional protein depletion, fluorescence and electron microscopy, and a mouse virulence model

   PMID:38191574

   Open questions at the time

   • ICMAP1's own contribution to rhoptry docking/discharge not directly tested
   • Molecular mechanism linking ICMT integrity to rhoptry docking not resolved
   • How the ICMAP proteins are organized on the ICMTs relative to one another not defined

• The direct functional role of ICMAP1 (as opposed to its relatives ICMAP2/ICMAP3) in ICMT scaffolding and rhoptry discharge remains to be established.
• No conditional loss-of-function or virulence data for ICMAP1 itself
• Interplay between ICMAP1 and ICMAP2/ICMAP3 on the ICMTs uncharacterized