Affinage · Plasmodium

CINCH

PF3D7_0407800 · protein CINCH

Annotated
2026-09-08
25 papers in source corpus 11 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CINCH (PF3D7_0407800) is an essential basal complex protein of Plasmodium falciparum that mediates precise segmentation (cytokinesis) during schizogony (PMID:31097714). It localizes to a ring at the leading edge of the inner membrane complex, colocalizing with PfMORN1, and this ring constricts as cytokinesis completes (PMID:31097714, PMID:34878291, PMID:37400439); conditional depletion of CINCH produces inviable conjoined daughter cells that contain components for multiple cells even though organelles form and divide normally, establishing that CINCH is specifically required for daughter-cell separation rather than organelle biogenesis (PMID:31097714). During schizogony the CINCH ring displays a punctate pattern that undergoes division events, and the number of CINCH-marked structures tracks the number of outer centriolar plaque cytoplasmic extensions, linking basal complex duplication to centriolar plaque branching (PMID:38108809). Full contraction of the CINCH ring requires clearance of organelles from the cytokinetic zone: in PfDyn2-deficient parasites, undivided mitochondria threaded through the rings physically block their constriction (PMID:39611847). CINCH serves as a scaffold and marker of the basal complex, with affinity purification identifying interaction partners including PfBTP2, PfBCP1, PfMORN1, PfMyoJ, and PfPPP8 (PMID:31097714, PMID:37400439); PfMyoJ and PfSLACR transiently colocalize with CINCH before segregating into a distinct posterior-cup subcompartment, revealing spatial compartmentalization within the basal complex (PMID:38829893). The molecular mechanism by which CINCH drives ring contraction and daughter-cell separation has not been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2019 High

    Established that CINCH is an essential cytokinesis factor by showing its loss uncouples daughter-cell segmentation from organelle division, answering whether the basal complex is required for the physical separation step of schizogony.

    Evidence Inducible knockdown with 3D electron microscopy reconstruction and immunofluorescence localization in P. falciparum 3D7

    PMID:31097714

    Open questions at the time
    • Does not reveal the biochemical activity by which CINCH drives separation
    • No structural model of the ring
    • Mechanism of force generation unresolved
  2. 2019 Medium

    Placed CINCH physically and spatially within the basal complex by identifying its interaction partners and showing it forms a constricting ring, addressing what molecular assembly CINCH belongs to.

    Evidence AP-MS co-immunoprecipitation of tagged CINCH and IFA colocalization with PfMORN1 in P. falciparum 3D7

    PMID:31097714

    Open questions at the time
    • Interactors identified by MS were not individually validated by reciprocal co-IP in this study
    • Direct versus indirect nature of each association unknown
    • Stoichiometry and architecture of the complex not defined
  3. 2023 Medium

    Linked basal complex duplication to the nuclear/centriolar cell-cycle machinery by showing CINCH ring number tracks centriolar plaque branching, addressing how basal complex biogenesis is coordinated with division.

    Evidence Ultrastructure expansion microscopy of smV5-tagged CINCH in P. falciparum 3D7

    PMID:38108809

    Open questions at the time
    • Molecular signal coupling CINCH duplication to centriolar plaques unknown
    • Single imaging method
    • Does not establish causality of the correlation
  4. 2023 Medium

    Extended the basal complex interactome and demonstrated dynamic expansion by using CINCH as bait to discover PfPPP8, addressing which additional components support ring behavior.

    Evidence Co-immunoprecipitation with CINCH as bait plus IFA and conditional knockdown of PfPPP8 in P. falciparum 3D7

    PMID:37400439

    Open questions at the time
    • No direct mechanistic follow-up on CINCH itself
    • Single lab
    • Functional interdependence of CINCH and PfPPP8 not tested
  5. 2024 Medium

    Showed that CINCH ring constriction is gated by organelle clearance, answering whether contraction can proceed while organelles remain in the cytokinetic zone.

    Evidence Live-cell fluorescence microscopy of mNeonGreen-tagged CINCH in a PfDyn2-deficient background of P. falciparum NF54attB

    PMID:39611847

    Open questions at the time
    • Does not identify the contractile motor driving CINCH ring constriction
    • Two biological replicates, single lab
    • Whether CINCH itself senses organelle position unknown
  6. 2024 Medium

    Revealed spatial compartmentalization of the basal complex by showing PfMyoJ and PfSLACR transiently colocalize with CINCH then form a distinct posterior cup, refining the substructure in which CINCH operates.

    Evidence U-ExM co-localization of endogenously tagged CINCH, PfMyoJ, and PfSLACR in P. falciparum

    PMID:38829893

    Open questions at the time
    • Functional consequence of the CINCH/posterior-cup separation not tested
    • How CINCH is retained in its subcompartment unknown
    • Single lab
  7. 2026 Medium

    Used CINCH as an epistatic marker to localize the BTP2-dependent defect upstream of ring contraction, establishing that the CINCH-containing ring retains contractile competence in BTP2 loss.

    Evidence IFA and expansion microscopy of endogenously tagged CINCH in BTP2 conditional knockout P. falciparum

    PMID:41706859

    Open questions at the time
    • Intrinsic contractile mechanism of CINCH not directly probed
    • Single lab
    • Relationship between BTP2 and CINCH assembly not fully resolved
  8. 2026 Medium

    Identified PfCHAKRA as required for correct positioning of CINCH-marked basal complexes, answering how apical-basal polarity of the ring is maintained during schizogony.

    Evidence U-ExM of smMyc-tagged CINCH in PfCHAKRA conditional knockdown P. falciparum, three biological replicates

    PMID:42135436

    Open questions at the time
    • Mechanism by which PfCHAKRA positions the CINCH ring unknown
    • Direct interaction between CINCH and PfCHAKRA not shown
    • Single lab
  9. 2025 Low

    Peripheral evidence placed CINCH near additional division machinery and under phosphoregulation, hinting at broader regulatory connections of the basal complex.

    Evidence PfAnchor IP-MS, PfFBXO1 TurboID proximity labeling, and PfPPM2-depletion phosphoproteomics in P. falciparum

    PMID:39915671 PMID:40410154 PMID:41309594

    Open questions at the time
    • All three are single-method associations without reciprocal or enzymatic validation
    • Proximity/pulldown captures non-direct associations
    • No specific CINCH phosphosite or its functional role defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The core question of how CINCH generates or transmits the contractile force that separates daughter cells, and its own biochemical activity, remains unresolved.
  • No defined molecular/enzymatic activity for CINCH
  • No structural model of the CINCH ring or its contraction mechanism
  • Direct force-generating partner of CINCH not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
PFANCHOR (LOW-CONFIDENCE, SINGLE PULLDOWN)PFBCP1PFBTP2PFFBXO1 (LOW-CONFIDENCE, PROXIMITY LABELING)PFMORN1PFMYOJPFPPP8PFSLACR
Complex memberships
Basal complex (contractile ring at the leading edge of the inner membrane complex)

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 CINCH (PF3D7_0407800) is an essential component of the basal complex in P. falciparum. Conditional depletion of CINCH causes formation of inviable conjoined daughter cells containing components for multiple cells, while parasite organelles form and divide normally, demonstrating that CINCH is required for precise segmentation (cytokinesis) during schizogony. Inducible knockdown with 3D electron microscopy reconstruction of phenotype; immunofluorescence localization Nature communications High 31097714
2019 Biochemical immunoprecipitation of CINCH identified multiple previously undescribed basal complex proteins as interaction partners, including PfBTP2, PfBCP1, PfMORN1, and PfMyoJ, establishing CINCH as a scaffold component of the basal complex protein complex. Affinity purification–mass spectrometry (co-immunoprecipitation of tagged CINCH followed by MS) Nature communications Medium 31097714
2019 CINCH colocalizes with PfMORN1 at the basal complex, forming a ring structure at the leading edge of the inner membrane complex during segmentation that constricts as cytokinesis completes, establishing its spatial position within the contractile ring. Immunofluorescence assay with co-localization of endogenously tagged CINCH and PfMORN1 Nature communications High 31097714 34878291 37400439
2023 Using ultrastructure expansion microscopy (U-ExM), CINCH was shown to display a punctate basal complex ring pattern during schizogony that undergoes division events visible as gaps in staining, and the number of CINCH-marked basal complex structures closely matched the number of outer centriolar plaque cytoplasmic extensions throughout schizogony, linking basal complex duplication to centriolar plaque branching. Ultrastructure expansion microscopy (U-ExM) with immunostaining of smV5-tagged CINCH eLife Medium 38108809
2023 PfPPP8, identified via immunoprecipitation with CINCH, is a basal complex protein required for uniform basal complex expansion; this established CINCH as bait for discovering additional basal complex components and confirmed the dynamic nature of the complex. Co-immunoprecipitation using CINCH as bait, followed by characterization of PfPPP8 by IFA and conditional knockdown Nature communications Medium 37400439
2024 Live-cell microscopy using a PfDyn2-PfCINCH-mNeonGreen dual reporter line showed that in PfDyn2-deficient parasites, CINCH-marked basal complex rings fail to fully contract because undivided mitochondria threaded through the rings physically block their constriction, demonstrating that CINCH ring contraction requires clearance of organelles from the cytokinetic zone. Live-cell fluorescence microscopy with mNeonGreen-tagged CINCH in PfDyn2-deficient background mBio Medium 39611847
2024 PfMyoJ and PfSLACR are recruited to the basal complex midway through segmentation and colocalize with CINCH upon recruitment, but then form a separate, more basal subcompartment (the posterior cup) distinct from the CINCH-marked region during contraction, revealing spatial compartmentalization within the basal complex. Ultrastructure expansion microscopy (U-ExM) with co-localization of endogenously tagged CINCH, PfMyoJ, and PfSLACR PLoS pathogens Medium 38829893
2026 CINCH-marked basal complexes assemble and are present in BTP2-knockout parasites but their contraction ability remains intact (the contractile defect is not in the CINCH-containing ring itself), and CINCH is used as a reference marker to show that BTP2 loss prevents daughter cell separation at a step upstream of contraction. Immunofluorescence assay and expansion microscopy using endogenously tagged CINCH as basal complex marker in BTP2 conditional knockout parasites Science advances Medium 41706859
2026 In PfCHAKRA-deficient parasites, CINCH-marked basal complexes assemble but lose their central positioning and appear as scattered structures at ectopic locations, demonstrating that PfCHAKRA is required for the spatial organization of CINCH-containing basal complexes and maintenance of apical–basal polarity during schizogony. Ultrastructure expansion microscopy (U-ExM) with smMyc-tagged CINCH as basal complex marker in PfCHAKRA conditional knockdown parasites Nature microbiology Medium 42135436
2025 Immunoprecipitation of PfAnchor identified CINCH as an enriched interacting protein, suggesting a physical association between the apicoplast fission adaptor PfAnchor and the basal complex component CINCH. Immunoprecipitation followed by mass spectrometry (PfAnchor as bait) Nature communications Low 41309594
2025 Proximity biotinylation (TurboID) of PfFBXO1 during schizogony identified CINCH among the significantly enriched proximal proteins, consistent with CINCH's known basal complex localization and indicating spatial proximity between PfFBXO1 and the basal complex. TurboID proximity labeling followed by streptavidin pull-down and mass spectrometry Communications biology Low 39915671
2025 CINCH was identified among the differentially phosphorylated proteins in PfPPM2-depleted parasites, indicating that phosphorylation state of CINCH is regulated (directly or indirectly) by the protein phosphatase PfPPM2 during asexual division. Phosphoproteomics of PfPPM2-depleted versus sufficient parasites Nature communications Low 40410154

Source papers

Stage 0 corpus · 25 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 An essential contractile ring protein controls cell division in Plasmodium falciparum. Nature communications 62 31097714
2024 Elucidating the spatio-temporal dynamics of the Plasmodium falciparum basal complex. PLoS pathogens 4 38829893
2026 Transmembrane proteins mediate basal complex assembly and individual daughter cell formation in malaria parasites. Science advances 0 41706859
2026 The apical polar ring is essential during the blood stage of Plasmodium falciparum. Nature microbiology 0 42135436
2025 PfFBXO1 is essential for inner membrane complex formation in Plasmodium falciparum during both asexual and transmission stages. Communications biology 0 39915671
2025 PfPPM2 signalling regulates asexual division and sexual conversion of human malaria parasite Plasmodium falciparum. Nature communications 0 40410154
2025 An essential adaptor for apicoplast fission and inheritance in malaria parasites. Nature communications 0 41309594
2024 The molecular mechanisms driving Plasmodium cell division. Biochemical Society transactions 0 38563493
2024 An inner membrane complex protein IMC1g in Plasmodium berghei is involved in asexual stage schizogony and parasite transmission. mBio 0 39576115
2024 The dynamin-related protein PfDyn2 is essential for both apicoplast and mitochondrial fission in Plasmodium falciparum. mBio 0 39611847
2023 Plasmodium schizogony, a chronology of the parasite's cell cycle in the blood stage. PLoS pathogens 0 36862652
2023 Same, same but different: Exploring Plasmodium cell division during liver stage development. PLoS pathogens 0 36996035
2023 A PPP-type pseudophosphatase is required for the maintenance of basal complex integrity in Plasmodium falciparum. Nature communications 0 37400439
2023 Essential function of alveolin PfIMC1g in the Plasmodium falciparum asexual blood stage. mBio 0 37712738
2023 Atlas of Plasmodium falciparum intraerythrocytic development using expansion microscopy. eLife 0 38108809
2022 Toxoplasma gondii's Basal Complex: The Other Apicomplexan Business End Is Multifunctional. Frontiers in cellular and infection microbiology 0 35573773
2022 Inner membrane complex proteomics reveals a palmitoylation regulation critical for intraerythrocytic development of malaria parasite. eLife 0 35775739
2022 Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites. Proceedings of the National Academy of Sciences of the United States of America 0 35972967
2021 The Dynamic Roles of the Inner Membrane Complex in the Multiple Stages of the Malaria Parasite. Frontiers in cellular and infection microbiology 0 33489940
2021 Malaria Parasite Schizont Egress Antigen-1 Plays an Essential Role in Nuclear Segregation during Schizogony. mBio 0 33688001
2021 The Ringleaders: Understanding the Apicomplexan Basal Complex Through Comparison to Established Contractile Ring Systems. Frontiers in cellular and infection microbiology 0 33954122
2021 The Basal Complex Protein PfMORN1 Is Not Required for Asexual Replication of Plasmodium falciparum. mSphere 0 34878291
2020 Three-dimensional ultrastructure of Plasmodium falciparum throughout cytokinesis. PLoS pathogens 0 32511279
2020 Fussing About Fission: Defining Variety Among Mainstream and Exotic Apicomplexan Cell Division Modes. Frontiers in cellular and infection microbiology 0 32582569
2019 Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite. Frontiers in cellular and infection microbiology 0 31824870