Affinage · Toxoplasma gondii

AC10

apical cap protein AC10 · UniProt A0A125YMU5

Annotated
2026-09-08
3 papers in source corpus 3 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AC10 is an essential structural component of the apical cap alveolin network in Toxoplasma gondii, required for the integrity of the apical complex and for the invasion-related secretory machinery (PMID:32379047). It localizes to the alveolin network intercalated between the subpellicular microtubules (SPMTs) at the apical cap, where it was identified as a partner of AC9 (PMID:32379047). AC10 is a foundational component of a trimeric AC9:AC10:ERK7 complex, forming multiple independent pairwise interactions with both AC9 and the kinase ERK7 that enable multivalent oligomerization; this scaffold concentrates ERK7 kinase activity in the apical cap to maintain apical complex integrity (PMID:35130732). Consistent with this scaffolding role, AC10 depletion phenocopies ERK7 depletion (PMID:34607461). Conditional loss of AC10 disorganizes the SPMTs, eliminating the apical polar ring and conoid, and blocks microneme secretion, host-cell invasion, and egress while leaving replication intact (PMID:32379047).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2020 High

    Establishing where AC10 acts and what it partners with was the entry point: BioID and expansion microscopy placed AC10 in the apical cap alveolin network between the subpellicular microtubules as an AC9 partner, defining it as a cytoskeletal apical-cap protein.

    Evidence BioID proximity ligation with AC9 and ultrastructure expansion microscopy in T. gondii

    PMID:32379047

    Open questions at the time
    • Molecular basis of the AC10–AC9 interaction not mapped at this stage
    • No functional consequence of localization established yet
  2. 2020 High

    Whether AC10 is functionally essential was answered by conditional depletion, which separated a structural/secretory role from replication and showed AC10 is required for microneme secretion, invasion, and egress.

    Evidence Conditional knockdown with microneme secretion, invasion, and egress assays in T. gondii

    PMID:32379047

    Open questions at the time
    • Does not distinguish direct structural role from downstream secretory signalling
    • Molecular step blocked in microneme secretion not defined
  3. 2020 High

    The structural basis of the invasion defect was resolved by ultrastructure: loss of AC10 disorganizes the SPMTs and eliminates the apical polar ring and conoid, establishing AC10 as required for apical complex architecture.

    Evidence Conditional knockdown with electron microscopy and U-ExM in T. gondii

    PMID:32379047

    Open questions at the time
    • Mechanism linking AC10 loss to SPMT disorganization unresolved
    • Whether AC10 stabilizes microtubules directly or via partners unknown
  4. 2021 High

    Placing AC10 in a defined pathway rather than a standalone role, comparative depletion showed AC10 loss phenocopies ERK7 kinase loss across structural and secretory readouts, linking a scaffold protein to a kinase.

    Evidence Conditional depletion with comparative proteomics, U-ExM, NHS-ester staining, and microneme secretion assays in T. gondii

    PMID:34607461

    Open questions at the time
    • Phenocopy does not by itself establish physical interaction
    • Direction of regulation between AC10 and ERK7 not defined here
  5. 2022 Medium

    The physical logic of the pathway was defined: deletion mapping and yeast two-hybrid showed AC10 makes multiple independent pairwise contacts with both AC9 and ERK7, establishing it as the foundational, multivalent hub of a trimeric AC9:AC10:ERK7 complex.

    Evidence Deletion analyses and yeast two-hybrid interaction mapping in T. gondii

    PMID:35130732

    Open questions at the time
    • No in vitro reconstitution or structure of the complex
    • Stoichiometry of the oligomerized complex not determined
  6. 2022 Medium

    The purpose of the scaffold was framed mechanistically: assembly of the multivalent complex into the IMC concentrates ERK7 kinase activity in the apical cap, and disrupting the interactions impairs apical complex maintenance.

    Evidence Deletion analyses, yeast two-hybrid, and functional complementation assays in T. gondii

    PMID:35130732

    Open questions at the time
    • Local ERK7 kinase activity concentration inferred from assembly, not measured by direct enzymatic reconstitution
    • ERK7 substrates at the apical cap not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AC10-mediated ERK7 concentration is translated into SPMT organization and apical polar ring/conoid assembly at the molecular level remains open.
  • No identified ERK7 substrates linking the complex to microtubule/APR/conoid integrity
  • No structural model of the assembled AC9:AC10:ERK7 complex
  • Mechanism coupling apical structure to microneme secretion undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
AC9ERK7
Complex memberships
AC9:AC10:ERK7 trimeric apical cap complex

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 AC10 localizes to the alveolin network intercalated between the subpellicular microtubules (SPMTs) at the apical cap, as identified by BioID as a partner of AC9 and confirmed by ultrastructure expansion microscopy (U-ExM). BioID proximity ligation, ultrastructure expansion microscopy (U-ExM) eLife High 32379047
2020 Conditional depletion of AC10 results in parasites that replicate normally but are defective in microneme secretion, fail to invade host cells, and cannot egress from infected cells, demonstrating an essential role for AC10 in these processes. Conditional knockdown (auxin-inducible degron or similar), invasion/egress assays, microneme secretion assay eLife High 32379047
2020 Loss of AC10 in mature parasites causes disorganization of the SPMTs leading to loss of the apical polar ring (APR) and conoid, establishing AC10 as structurally required for apical complex integrity. Conditional knockdown, electron microscopy, ultrastructure expansion microscopy (U-ExM) eLife High 32379047
2021 Depletion of AC10 phenocopies depletion of ERK7 kinase: both lead to loss of the APR, disorganization of SPMTs, severe impairment of microneme secretion, and accumulation of microneme proteins, placing AC10 and ERK7 in the same functional pathway for apical complex stability. Conditional depletion, comparative proteomics, U-ExM, NHS-ester staining, microneme secretion assay mBio High 34607461
2022 AC10 is a foundational component of the AC9:AC10:ERK7 trimeric complex in the apical cap, forming multiple independent pairwise interactions with both AC9 and ERK7, enabling multivalent oligomerization of the complex. Deletion analyses, yeast two-hybrid experiments mBio Medium 35130732
2022 The multivalent AC9:AC10:ERK7 complex assembly into the cytoskeletal IMC serves as a structural scaffold that concentrates ERK7 kinase activity in the apical cap; disruption of interactions among these proteins impairs apical complex maintenance. Deletion analyses, yeast two-hybrid experiments, functional complementation assays mBio Medium 35130732

Source papers

Stage 0 corpus · 3 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Essential function of the alveolin network in the subpellicular microtubules and conoid assembly in Toxoplasma gondii. eLife 82 32379047
2021 Revisiting the Role of Toxoplasma gondii ERK7 in the Maintenance and Stability of the Apical Complex. mBio 28 34607461
2022 Multivalent Interactions Drive the Toxoplasma AC9:AC10:ERK7 Complex To Concentrate ERK7 in the Apical Cap. mBio 21 35130732