Affinage · Toxoplasma gondii

IMC3

alveolin domain containing intermediate filament IMC3 · UniProt A0A125YIN2

Annotated
2026-09-11
10 papers in source corpus 7 papers cited in narrative 7 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IMC3 (TgIMC3/ALV3) is an alveolin domain-containing intermediate filament-like protein of the Toxoplasma gondii inner membrane complex (IMC) cytoskeleton, contributing to the architecture of the subpellicular filamentous network (PMID:15279956, PMID:39264987). It is present in both mother and daughter cytoskeletons during asexual tachyzoite division and in sporozoites, but is absent from developing macro- and microgametocytes, marking stage-specific localization dynamics across the life cycle (PMID:29062899). IMC3 is strongly enriched in forming daughter buds during endodyogeny and is among the earliest-recruited alveolins, loaded ahead of IMC1 and IMC4 (PMID:40590555, PMID:42113865); because bud-associated intensity is high in newly formed daughters and decays without further division, the protein has been exploited as a quantitative reporter of replication dynamics (PMID:26350965). Architecturally, IMC3 builds the network through defined protein-protein contacts: its C-terminal domain is required for binding the essential IMC protein ILP1, while its alveolin domain mediates interaction with IMC6, providing direct evidence that the alveolin domain drives filament formation within the network (PMID:31584943, PMID:39264987). Beyond these localization and interaction findings, no further mechanistic detail for IMC3 has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2004 Medium

    Establishing where IMC3 acts: it was needed to know whether this novel protein was part of the IMC, which was answered by localizing it to that compartment.

    Evidence YFP-genomic DNA fusion library screen with flow cytometry and fluorescence microscopy against compartment markers in T. gondii

    PMID:15279956

    Open questions at the time
    • No functional role or interacting partners defined
    • No division-stage dynamics characterized
  2. 2015 Medium

    IMC3 bud enrichment tracks division, establishing it as a quantitative readout of endodyogeny timing in vivo.

    Evidence Immunofluorescence of purified tissue cysts with quantitative intensity analysis over time (BradyCount 1.0) in bradyzoites

    PMID:26350965

    Open questions at the time
    • Intensity decay mechanism not defined
    • Does not test whether IMC3 is required for division
  3. 2017 Medium

    Whether IMC3 localization is constant across the life cycle was open; showing presence in tachyzoites and sporozoites but absence in gametocytes defined stage-specific dynamics.

    Evidence Immunofluorescence microscopy across tachyzoites, gametocytes, and sporozoites with stage-specific markers in T. gondii

    PMID:29062899

    Open questions at the time
    • Functional consequence of absence in gametocytes unknown
    • Regulation of stage-specific expression not defined
  4. 2019 High

    Moving from localization to molecular architecture, IMC3 was shown to make a defined contact within the IMC, binding ILP1 through its C-terminal domain.

    Evidence Photoactivatable unnatural amino acid crosslinking in situ, mass spectrometry, and deletion mapping in T. gondii

    PMID:31584943

    Open questions at the time
    • Functional consequence of the IMC3-ILP1 interaction not tested
    • Structural basis of the C-terminal contact not resolved
  5. 2024 High

    The role of the alveolin domain was clarified by demonstrating it mediates the IMC3-IMC6 interaction, providing direct evidence that this domain drives filament formation in the subpellicular network.

    Evidence Unnatural amino acid photoreactive crosslinking targeted to the alveolin domain, mass spectrometry, and deletion analyses in T. gondii

    PMID:39264987

    Open questions at the time
    • Filament structure not directly visualized
    • Functional requirement of the interaction for network integrity not tested
  6. 2025 Medium

    The temporal order of IMC assembly was resolved by placing IMC3 among the earliest alveolins recruited to daughter buds, ahead of IMC1 and IMC4.

    Evidence Live fluorescence microscopy with epitope-tagged proteins and cell cycle reporters (ToxoFUCCIS, mCherry-TgIMC3), comparative timing analysis in T. gondii

    PMID:40590555 PMID:42113865

    Open questions at the time
    • Mechanism directing early IMC3 recruitment unknown
    • Whether early recruitment is required for later assembly not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
ILP1 (VIA IMC3 C-TERMINAL DOMAIN)IMC6 (VIA IMC3 ALVEOLIN DOMAIN)
Complex memberships
Inner membrane complex subpellicular filamentous network

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 IMC3 was identified as a novel inner membrane complex (IMC) protein in Toxoplasma gondii, with subcellular localization to the IMC confirmed by fluorescence microscopy using a YFP-genomic DNA fusion library screened by flow cytometry; the protein is conserved among Apicomplexa. YFP-genomic DNA fusion library screen, flow cytometry, fluorescence microscopy with compartment-specific markers Molecular and biochemical parasitology Medium 15279956
2017 IMC3 is present in both mother and daughter cytoskeletons during asexual division of tachyzoites, with strong enrichment in daughter buds; IMC3 is absent in developing macro- and microgametocytes but present in sporozoites, indicating stage-specific localization dynamics across the life cycle. Immunofluorescence microscopy across multiple life cycle stages (tachyzoites, gametocytes, sporozoites) with stage-specific markers mSphere Medium 29062899
2019 IMC3 physically interacts with the essential IMC protein ILP1 via ILP1's C-terminal coiled-coil domain; the C-terminal domain of IMC3 is necessary for binding to ILP1, as mapped by photoactivatable unnatural amino acid (UAA) crosslinking. Photoactivatable unnatural amino acid (UAA) crosslinking in native intracellular environment, mass spectrometry, deletion mapping of binding interfaces PLoS biology High 31584943
2024 IMC3 physically interacts with IMC6 through the alveolin domain, as demonstrated by unnatural amino acid photoreactive crosslinking; this interaction provides direct evidence that the alveolin domain mediates filament formation within the subpellicular network (SPN) of the IMC cytoskeleton. Unnatural amino acid photoreactive crosslinking to the alveolin domain, mass spectrometry-based partner identification, deletion analyses PLoS biology High 39264987
2015 TgIMC3 intensity is strongly elevated in newly formed/forming daughter buds during bradyzoite endodyogeny and decays over time in the absence of further division; this differential intensity was exploited as a reporter to capture and quantify bradyzoite replication dynamics in vivo within tissue cysts. Immunofluorescence microscopy of purified tissue cysts with custom imaging software (BradyCount 1.0), quantitative intensity analysis over time in vivo mBio Medium 26350965
2025 IMC3 is recruited to forming daughter buds earlier than IMC1 during endodyogeny, as determined by co-expression timing analysis; mCherry-tagged TgIMC3 was used as a budding indicator in the ToxoFUCCIS cell cycle indicator system to define the onset of cytokinesis within the composite cell cycle phase. Live fluorescence microscopy, auxin-induced degradation system, co-expression of TgPCNA1-NeonGreen and mCherry-TgIMC3 as cell cycle phase reporters mBio Medium 40590555
2025 IMC3 is loaded onto forming daughter buds earlier than IMC1 and IMC4 during endodyogeny, placing IMC3 among the early-recruited alveolins (along with IMC6 and IMC10) in the temporal hierarchy of IMC assembly. Fluorescence microscopy of epitope-tagged proteins, comparative expression timing analysis across IMC proteins during daughter bud formation PLoS pathogens Medium 42113865

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Novel Approaches Reveal that Toxoplasma gondii Bradyzoites within Tissue Cysts Are Dynamic and Replicating Entities In Vivo. mBio 166 26350965
2004 Fluorescent protein tagging in Toxoplasma gondii: identification of a novel inner membrane complex component conserved among Apicomplexa. Molecular and biochemical parasitology 84 15279956
2017 Differential Roles for Inner Membrane Complex Proteins across Toxoplasma gondii and Sarcocystis neurona Development. mSphere 50 29062899
2019 A photoactivatable crosslinking system reveals protein interactions in the Toxoplasma gondii inner membrane complex. PLoS biology 33 31584943
2013 Isospora suis in an epithelial cell culture system - an in vitro model for sexual development in coccidia. PloS one 29 23861983
2024 Alveolin proteins in the Toxoplasma inner membrane complex form a highly interconnected structure that maintains parasite shape and replication. PLoS biology 10 39264987
2025 Deciphering cell cycle organization of Toxoplasma endodyogeny. mBio 5 40590555
2023 The Toxoplasma subpellicular network is highly interconnected and defines parasite shape for efficient motility and replication. bioRxiv : the preprint server for biology 3 37609316
2026 Toxoplasma IMC1 is a central component of the subpellicular network and plays critical roles in parasite morphology, replication, and infectivity. PLoS pathogens 0 42113865
2025 Toxoplasma IMC1 is a central component of the subpellicular network and plays critical roles in parasite morphology, replication, and infectivity. bioRxiv : the preprint server for biology 0 40501855