Affinage · Plasmodium

PIP1

PF3D7_1355600 · PhIL1 interacting protein PIP1

Annotated
2026-09-08
5 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIP1 (PF3D7_1355600) is a component of the PhIL1-associated complex within the inner membrane complex (IMC) of Plasmodium falciparum, required for correct membrane trafficking and IMC formation across both sexual and asexual stages (PMID:28985225, PMID:34324609). In gametocytes, genetic disruption of PIP1 ablates cell elongation and prevents formation of transmission-ready mature gametocytes, with failure to form an enveloping IMC and marked swelling of the digestive vacuole (PMID:28985225). In merozoites, PIP1 associates with the PhIL1 complex, and its conditional downregulation causes defects in merozoite segmentation, abrogates reorientation/gliding, and blocks erythrocyte invasion while leaving initial attachment to red blood cells intact (PMID:34324609). Beyond its membership in the PhIL1 complex and these stage-specific IMC and invasion phenotypes, no further molecular mechanism for PIP1 has been characterized in the available corpus.

Mechanistic history

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

    Establishing whether PIP1 has a role in sexual-stage development, its disruption revealed a requirement for gametocyte maturation and IMC biogenesis, implicating it in membrane trafficking during transmission-stage differentiation.

    Evidence Genetic knockout with ultrastructural readout by super-resolution and electron microscopy, plus immunoprecipitation/mass spectrometry, in P. falciparum gametocytes

    PMID:28985225

    Open questions at the time
    • The molecular activity of PIP1 within the IMC is not defined
    • How PIP1 loss mechanistically causes digestive vacuole swelling is unresolved
    • The direct binding partners of PIP1 versus co-purifying complex members are not distinguished
  2. 2021 High

    Extending PIP1's role to asexual blood stages, conditional knockdown established it as a PhIL1-complex member required for merozoite segmentation, reorientation/gliding, and invasion but not initial attachment, separating its function from the earliest adhesion step.

    Evidence Conditional knockdown with invasion and reorientation/gliding assays and co-immunoprecipitation with PhIL1 in P. falciparum merozoites

    PMID:34324609

    Open questions at the time
    • Whether PIP1 acts structurally or as a trafficking adaptor within the PhIL1 complex is unknown
    • The stoichiometry and architecture of PIP1 within the PhIL1 complex is not resolved
    • No structural model or defined molecular activity is available

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biochemical activity by which PIP1 contributes to IMC formation and membrane trafficking, and its direct molecular partners within the PhIL1 complex, remain undefined.
  • No enzymatic or structural activity assigned to PIP1
  • Direct versus indirect interactions within the PhIL1 complex not mapped
  • Mechanism linking PIP1 to reorientation/gliding is not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
PHIL1
Complex memberships
PhIL1-associated complex

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 PIP1 (PF3D7_1355600) is a component of the gametocyte inner membrane complex (IMC) of P. falciparum. Genetic disruption of PIP1 ablates gametocyte elongation and prevents formation of transmission-ready mature gametocytes, accompanied by failure to form an enveloping IMC and marked swelling of the digestive vacuole, indicating PIP1 is required for correct membrane trafficking during sexual stage development. Super-resolution optical and electron microscopy for ultrastructure; genetic disruption (knockout) with phenotypic readout (elongation failure, IMC absence, digestive vacuole swelling); immunoprecipitation and mass spectrometry for interactome PLoS pathogens High 28985225
2021 PIP1 (PF3D7_1355600, referred to as PfPhIP in this study) is an uncharacterized protein that associates with the PhIL1 complex in the inner membrane complex of P. falciparum merozoites. Conditional downregulation of PIP1 results in significant defects in merozoite segmentation, abrogation of merozoite reorientation/gliding, and failure to invade host erythrocytes, while initial attachment to host RBCs was not affected. Experimental genetics (conditional knockdown/knockdown by inducible system); invasion assay; reorientation/gliding assays; co-immunoprecipitation with PhIL1 to establish complex membership PLoS pathogens High 34324609

Source papers

Stage 0 corpus · 5 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Disrupting assembly of the inner membrane complex blocks Plasmodium falciparum sexual stage development. PLoS pathogens 65 28985225
2021 Identification of novel inner membrane complex and apical annuli proteins of the malaria parasite Plasmodium falciparum. Cellular microbiology 33 33830607
2017 Photosensitized INA-Labelled protein 1 (PhIL1) is novel component of the inner membrane complex and is required for Plasmodium parasite development. Scientific reports 25 29138437
2021 Plasmodium falciparum PhIL1-associated complex plays an essential role in merozoite reorientation and invasion of host erythrocytes. PLoS pathogens 10 34324609
2024 An inner membrane complex protein IMC1g in Plasmodium berghei is involved in asexual stage schizogony and parasite transmission. mBio 6 39576115