Affinage · Toxoplasma gondii

RAB1B

putative small GTP binding protein rab1a · UniProt A0A125YLS2

Annotated
2026-09-10
3 papers in source corpus 2 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TgRab1B is a prenylated small GTPase that functions as a vesicular trafficking regulator in Toxoplasma gondii, acting at the intersection of the trans-Golgi network and endosome-like compartments (PMID:37548452). Its conditional depletion rapidly disrupts secretory trafficking to the rhoptry bulb, establishing a direct role in exocytic sorting of rhoptry proteins (PMID:37548452). Rab1B additionally regulates endocytic trafficking of host-derived material, and was identified through prenylated-proteome screening as one of four prenylated proteins required for this endocytic process, with prenylation required for its stability and activity (PMID:37548452). Beyond these trafficking roles, no direct biochemical characterization of Rab1B's GTPase cycle, effectors, or guanine-nucleotide exchange machinery has been reported in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2023 Medium

    It was unknown which regulator coordinates secretory sorting to the rhoptry bulb; conditional depletion of Rab1B showed it operates at the TGN/endosome intersection to control rhoptry protein sorting, defining an exocytic trafficking function.

    Evidence CRISPR/Cas9 tetracycline-inducible knockdown with confocal localization and rhoptry sorting readout in T. gondii

    PMID:37548452

    Open questions at the time
    • No effector or GEF/GAP partners identified
    • GTPase cycle not directly measured
    • Mechanism linking Rab1B to rhoptry cargo selection unresolved
  2. 2023 Medium

    Whether Rab1B also acts in the endocytic direction and how prenylation contributes was unknown; functional screening of prenylated candidates showed Rab1B is required for endocytic uptake of host-derived material and that prenylation regulates its stability/activity.

    Evidence Click-chemistry prenylated proteome profiling, CRISPR knockdown, and host GFP acquisition endocytic assay in T. gondii

    PMID:37548452

    Open questions at the time
    • Prenyltransferase acting on Rab1B not defined
    • Whether endocytic and exocytic roles are separable is unclear
    • No structural basis for prenylation-dependent stability
  3. 2023 Low

    The broader organellar and metabolic consequences of Rab1B loss were uncharacterized; multi-omics after depletion linked Rab1B to biogenesis of multiple secretory organelles and to fatty acid and TCA metabolism, consistent with a role in endocytic nutrient scavenging.

    Evidence Conditional knockdown with transmission electron microscopy, RNA-seq, and non-targeted metabolomics in T. gondii

    PMID:37941035

    Open questions at the time
    • Metabolic links are correlative from omics, not biochemically reconstituted
    • Direct versus indirect effects on organelle biogenesis not distinguished
    • Causal path from trafficking defect to metabolic change unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular machinery of Rab1B — its GTPase cycle regulators, effectors, and direct cargo interactions — remains uncharacterized in the available corpus.
  • No effectors or regulators identified
  • No structural data
  • GTP/GDP cycling not measured directly

Mechanism profile

Synthesis pass · controlled-vocabulary classification
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 Conditional knockdown of Rab1B in T. gondii caused a rapid defect in secretory trafficking to the rhoptry bulb, establishing a role for Rab1B at a trafficking intersection between the trans-Golgi network and endosome-like compartments for rhoptry protein sorting. CRISPR/Cas9 conditional knockdown (tetracycline-inducible TATi/Ty-Rab1B), confocal imaging localization to trans-Golgi network and endosome-like compartments, host GFP acquisition endocytic trafficking assay mBio Medium 37548452
2023 Rab1B regulates endocytic trafficking of host-derived material (GFP vesicles) in T. gondii; knockdown identified it as one of four prenylated proteins required for this process, and protein prenylation was shown to regulate the stability/activity of Rab1B. Alkyne-labeled click chemistry prenylated proteome characterization, CRISPR/Cas9 genome editing, host GFP acquisition endocytic trafficking assay, functional screening of 23 prenylated candidates mBio Medium 37548452
2023 Depletion of Rab1B caused strong disorganization of endo-membranes and differentially expressed genes associated with rhoptry, microneme, endoplasmic reticulum, and Golgi apparatus organelles, indicating Rab1B is involved in biogenesis of multiple secretory organelles. Multi-omics analyses also linked Rab1B to fatty acid biogenesis (myrisoleic acid, oleic acid) and TCA cycle metabolism, consistent with its role in endocytic nutrient scavenging. Tetracycline-inducible conditional knockdown, transmission electron microscopy, high-throughput transcriptomics (RNA-seq), non-targeted metabolomics, qRT-PCR validation, correlation analysis of DEMs and DEGs Parasites & vectors Low 37941035

Source papers

Stage 0 corpus · 3 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 Functional screening reveals Toxoplasma prenylated proteins required for endocytic trafficking and rhoptry protein sorting. mBio 13 37548452
2023 Transcriptomic and metabolomic analyses reveal the essential nature of Rab1B in Toxoplasma gondii. Parasites & vectors 4 37941035
2024 Deciphering protein prenylation in endocytic trafficking in Toxoplasma gondii. mBio 1 38407123