Affinage · Toxoplasma gondii

CRK6

CDK-related protein kinase CRK6 · UniProt S8GII9

Annotated
2026-09-11
6 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TgCrk6 is an essential Cdk-related kinase in Toxoplasma gondii tachyzoites that governs mitotic spindle function and the spindle assembly checkpoint (SAC) (PMID:28671988, PMID:35130726). Conditional knockdown of TgCrk6 arrests tachyzoite growth and produces mitotic defects consistent with a loss of spindle function (PMID:28671988). TgCrk6 acts as the kinase partner of the parasite-specific atypical cyclin TgCyc1, and this stable TgCrk6/TgCyc1 complex controls metaphase by regulating the centromere-associated network, with knockdown of either component yielding identical mitotic defects (PMID:35130726).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2017 Medium

    Establishing whether TgCrk6 has a cell-cycle role defined its function as an essential regulator of mitotic spindle integrity, and its failure to bind any tested cyclin raised the question of how it is temporally controlled.

    Evidence Conditional tet-OFF knockdown with mitotic phenotyping and co-IP testing cyclin interactions in T. gondii

    PMID:28671988

    Open questions at the time
    • No cyclin partner identified at this stage (negative co-IP)
    • Direct kinase substrates not defined
    • Molecular basis of the spindle defect unresolved
  2. 2022 High

    Identifying TgCyc1 as the binding partner resolved the earlier orphan-kinase puzzle and defined the TgCrk6/TgCyc1 complex as a metaphase regulator that specifically controls the SAC via the centromere-associated network.

    Evidence Reciprocal co-IP/proteomics, conditional knockdown of both components with identical phenotypes, and global phosphoproteomics in T. gondii

    PMID:35130726

    Open questions at the time
    • Direct phosphorylation substrates within the centromere network not individually validated
    • Structural basis of the atypical cyclin-kinase interaction unknown
    • Mechanism by which the complex enforces checkpoint arrest not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
TGCYC1 (PARASITE-SPECIFIC ATYPICAL CYCLIN)
Complex memberships
TgCrk6/TgCyc1 kinase-cyclin complex

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 TgCrk6 is essential for tachyzoite growth and is required for spindle function during mitosis; conditional tet-OFF knockdown of TgCrk6 caused mitotic defects consistent with a spindle function role. TgCrk6 did not interact with any tested cyclin, suggesting it may not require a cyclin timing mechanism. Conditional tet-OFF mutant generation, phenotypic analysis of mitotic structures, co-immunoprecipitation (negative result for cyclin interaction) PLoS pathogens Medium 28671988
2022 TgCrk6 forms a stable complex with a parasite-specific atypical cyclin TgCyc1 (previously orphaned). Conditional knockdown of either TgCrk6 or TgCyc1 produces identical mitotic defects, demonstrating cooperative action. The TgCrk6/TgCyc1 complex regulates metaphase and controls the spindle assembly checkpoint (SAC), specifically controlling the centromere-associated network. Global phosphoproteomics showed that Toxoplasma metaphase is regulated by CDK, MAPK, and Aurora kinases, with TgCrk6/TgCyc1 specifically controlling centromere-associated processes. Co-immunoprecipitation/proteomics to identify cyclin partner TgCyc1; conditional expression models; quantitative fluorescence microscopy; global phosphoproteomics mBio High 35130726

Source papers

Stage 0 corpus · 6 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors. Chemistry & biology 202 10873834
2004 Protein kinases as targets for anti-parasitic chemotherapy. Biochimica et biophysica acta 113 15023358
2008 The cell cycle and Toxoplasma gondii cell division: tightly knit or loosely stitched? International journal for parasitology 82 18703066
2017 Checkpoints of apicomplexan cell division identified in Toxoplasma gondii. PLoS pathogens 59 28671988
2005 Characterization of two T. gondii CK1 isoforms. Molecular and biochemical parasitology 26 15811523
2022 Novel CRK-Cyclin Complex Controls Spindle Assembly Checkpoint in Toxoplasma Endodyogeny. mBio 17 35130726