Affinage · Toxoplasma gondii

ApiAT5

transporter, major facilitator family protein · UniProt A0A125YHI0

Annotated
2026-09-08
2 papers in source corpus 2 papers cited in narrative 4 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TgApiAT5-3 is a plasma membrane-localized major facilitator superfamily amino acid transporter that governs aromatic and large neutral amino acid homeostasis in Toxoplasma gondii tachyzoites, functioning as an exchanger with particular importance for L-tyrosine scavenging (PMID:30742695, PMID:30402958). Its transport activity is modulated by calcium signalling: TgCDPK3 phosphorylates the transporter at serine 56, an event that is beneficial but not strictly required for tyrosine import (PMID:30402958). Conditional loss of apiAT5-3 triggers transcriptional upregulation of ribosomal subunits without induction of compensatory transporters, followed by parasite death, establishing the transporter as essential for survival and for intracellular growth and virulence of the tachyzoite stage (PMID:30402958, PMID:30742695).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2018 High

    Establishing that TgApiAT5-3 is a tyrosine transporter under kinase control connected amino acid uptake to calcium signalling in the parasite.

    Evidence phosphoproteomics of WT vs ΔTgCDPK3, S56A site-directed mutagenesis, conditional knockout, metabolomics, and heterologous expression in T. gondii

    PMID:30402958

    Open questions at the time
    • Functional consequence of the S56 phosphorylation on transporter kinetics beyond a 'beneficial' effect is not resolved
    • Structural basis of substrate recognition and the exchange mechanism is undefined
    • Whether other kinases or signals regulate the transporter is unknown
  2. 2018 Medium

    Conditional depletion showed the transporter is genuinely essential rather than redundant, with no compensatory transporter induction masking its loss.

    Evidence conditional knockout of apiAT5-3 with transcriptomic profiling in T. gondii

    PMID:30402958

    Open questions at the time
    • Mechanistic link between transporter loss, ribosomal subunit upregulation, and cell death is not defined
    • Single-lab result
  3. 2019 High

    Placing TgApiAT5-3 within the ApiAT transporter family defined it as a plasma membrane exchanger for aromatic and large neutral amino acids critical to amino acid homeostasis and virulence.

    Evidence heterologous expression, plasma membrane localization assays, and loss-of-function intracellular growth and virulence phenotyping in T. gondii

    PMID:30742695

    Open questions at the time
    • Full substrate range and directionality of exchange beyond tyrosine not fully mapped
    • Contribution to virulence in vivo across life-cycle stages not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How S56 phosphorylation mechanistically tunes transport, and how tyrosine deprivation is sensed to drive the lethal ribosomal response, remain unresolved.
  • No structural model of the transporter or its substrate-binding site
  • Mechanism coupling nutrient loss to ribosomal transcriptional response undefined
  • No data outside the tachyzoite stage

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
TGCDPK3 (PHOSPHORYLATES TGAPIAT5-3 AT SERINE 56)

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 TgApiAT5-3 is a plasma membrane-localized amino acid transporter that functions as an exchanger for aromatic and large neutral amino acids, with particular importance for L-tyrosine scavenging and amino acid homeostasis in T. gondii tachyzoites. Functional characterization of ApiAT family transporters including heterologous expression, plasma membrane localization assays, and loss-of-function studies with intracellular growth phenotyping PLoS pathogens High 30742695
2018 ApiAT5-3 (TgApiAT5-3) is a tyrosine transporter of the major facilitator superfamily that is phosphorylated at serine 56 by TgCDPK3 upon induction of calcium signalling; this phosphorylation is beneficial but not essential for tyrosine import. Phosphoproteomic comparison of WT vs. ΔTgCDPK3 parasites; site-directed mutagenesis (S56A); conditional knockout; metabolomics; heterologous expression Molecular microbiology High 30402958
2018 Conditional knockout of apiAT5-3 results in transcriptional upregulation of most ribosomal subunits (but no alternative transporters) and subsequent parasite death, demonstrating that ApiAT5-3 is essential for parasite survival. Conditional knockout of apiAT5-3 with transcriptomic analysis of resulting phenotype Molecular microbiology Medium 30402958
2019 TgApiAT5-3 is critical for parasite virulence, as demonstrated by loss-of-function studies showing its importance for intracellular growth of the tachyzoite stage. Loss-of-function genetic analysis with intracellular growth and virulence phenotyping PLoS pathogens Medium 30742695

Source papers

Stage 0 corpus · 2 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 The tyrosine transporter of Toxoplasma gondii is a member of the newly defined apicomplexan amino acid transporter (ApiAT) family. PLoS pathogens 46 30742695
2018 Characterisation of the Toxoplasma gondii tyrosine transporter and its phosphorylation by the calcium-dependent protein kinase 3. Molecular microbiology 16 30402958