Affinage · Toxoplasma gondii

ISP2

IMC sub-compartment protein ISP2 · UniProt A0A125YYN0

Annotated
2026-09-11
10 papers in source corpus 1 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ISP2 is an inner membrane complex (IMC) sub-compartment protein of Toxoplasma gondii that acts as a scaffolding factor required for daughter-cell formation during endodyogeny (PMID:20844581). It localizes specifically to the central sub-compartment of the IMC through an N-terminal targeting signal that depends on coordinated myristoylation and palmitoylation for membrane anchoring (PMID:20844581). Its sub-compartment identity is enforced hierarchically: the related protein ISP1 gates ISP2 away from the apical cap, and disruption of ISP1 relocalizes ISP2 to the apical cap through a mechanism requiring the ISP1 C-terminal domain (PMID:20844581). Loss of ISP2 produces severe defects in daughter-cell formation, establishing its essential role in coordinating parasite replication (PMID:20844581).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2010 High

    Establishing where ISP2 resides and how it is anchored addressed how the IMC is partitioned into sub-compartments and defined a lipid-dependent targeting mechanism.

    Evidence Fluorescence microscopy with N-terminal targeting analysis and site-directed mutagenesis of predicted myristoylation/palmitoylation sites in T. gondii

    PMID:20844581

    Open questions at the time
    • The specific enzymes executing the lipid modifications were not identified in this study
    • Direct binding partners in the central sub-compartment were not defined
  2. 2010 High

    Testing whether sub-compartment identity is imposed by other ISP proteins revealed a hierarchical gatekeeping system in which ISP1 restricts ISP2 to the central region.

    Evidence Genetic knockout of ISP1 with fluorescence readout of ISP2 localization plus ISP1 domain-deletion analysis in T. gondii

    PMID:20844581

    Open questions at the time
    • Molecular basis of ISP1-mediated exclusion (direct interaction vs indirect crowding) not resolved
    • Which ISP1 C-terminal residues mediate ISP2 exclusion not mapped
  3. 2010 High

    Determining the consequence of ISP2 loss assigned a functional role in replication, showing ISP2 is required for proper daughter-cell formation during endodyogeny.

    Evidence Gene disruption of ISP2 with phenotypic analysis by fluorescence and electron microscopy in T. gondii

    PMID:20844581

    Open questions at the time
    • The molecular scaffolding activity underlying the defect was not identified
    • Interacting components of the daughter-cell machinery not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
ISP1ISP3

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 ISP2 localizes to the central sub-compartment of the Toxoplasma gondii IMC, and its targeting is dependent on N-terminal residues predicted for coordinated myristoylation and palmitoylation. Fluorescence microscopy, N-terminal targeting sequence analysis, site-directed mutagenesis of lipid modification sites PLoS pathogens High 20844581
2010 Disruption of ISP1 causes dramatic relocalization of ISP2 (and ISP3) from the central IMC region to the apical cap, demonstrating that ISP1 acts as a gatekeeper that hierarchically restricts ISP2 to its sub-compartment through its C-terminal region (beyond the N-terminal targeting domain). Genetic knockout of ISP1 followed by fluorescence microscopy of ISP2 localization; deletion analysis of ISP1 domains PLoS pathogens High 20844581
2010 Loss of ISP2 results in severe defects in daughter cell formation during endodyogeny, establishing a functional role for ISP2 in coordinating Toxoplasma replication. Gene disruption (knockout) of ISP2 with phenotypic analysis of daughter cell formation by fluorescence and electron microscopy PLoS pathogens High 20844581

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 A novel family of Toxoplasma IMC proteins displays a hierarchical organization and functions in coordinating parasite division. PLoS pathogens 192 20844581
2012 Toxoplasma ISP4 is a central IMC sub-compartment protein whose localization depends on palmitoylation but not myristoylation. Molecular and biochemical parasitology 44 22659420
2016 Virus-Like Nanoparticle Vaccine Confers Protection against Toxoplasma gondii. PloS one 33 27548677
2011 Subcellular antigen location influences T-cell activation during acute infection with Toxoplasma gondii. PloS one 33 21829561
2014 Identification and characterization of Toxoplasma SIP, a conserved apicomplexan cytoskeleton protein involved in maintaining the shape, motility and virulence of the parasite. Cellular microbiology 28 25088010
2016 Cross-protection induced by Toxoplasma gondii virus-like particle vaccine upon intraperitoneal route challenge. Acta tropica 15 27586039
2021 A Novel Toxoplasma Inner Membrane Complex Suture-Associated Protein Regulates Suture Protein Targeting and Colocalizes with Membrane Trafficking Machinery. mBio 12 34634933
2025 Co-dependent formation of the Toxoplasma gondii subpellicular microtubules and inner membrane skeleton. mBio 11 40801525
2009 Toxoplasma gondii: further studies on the subpellicular network. Memorias do Instituto Oswaldo Cruz 11 19820829
2024 Apical annuli are specialised sites of post-invasion secretion of dense granules in Toxoplasma. eLife 10 38270431