Affinage · Toxoplasma gondii

DHHC14

DHHC zinc finger domain-containing protein · UniProt A0A125YY95

Annotated
2026-09-10
1 papers in source corpus 1 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TgDHHC14 is an inner membrane complex (IMC)-resident member of the DHHC-CRD palmitoyl acyltransferase (PAT) family in Toxoplasma gondii. Conditional disruption of TgDHHC14 causes rapid collapse of the IMC in developing daughter cells, establishing its acyltransferase function as required for IMC biogenesis during daughter-cell formation (PMID:32329212). TgDHHC14 acts sequentially with TgDHHC2 on distinct IMC substrates: TgDHHC2 palmitoylates TgISP1/3 and TgIAP1/2, whose membrane association is lost upon TgDHHC2 depletion but is unaffected by TgDHHC14 depletion, indicating that TgDHHC14 modifies a separate set of substrates at a different stage of IMC sub-compartment formation (PMID:32329212). The direct palmitoylation substrates of TgDHHC14 have not been identified in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2020 High

    It was unknown which cellular structure TgDHHC14 maintains; conditional disruption combined with imaging localized TgDHHC14 to the IMC and showed its loss causes rapid IMC collapse in developing daughters, establishing it as an IMC-resident PAT required for IMC biogenesis.

    Evidence Conditional loss-of-function, subcellular imaging, and morphological phenotype analysis in T. gondii tachyzoites

    PMID:32329212

    Open questions at the time
    • Direct palmitoylation substrates of TgDHHC14 not identified
    • Enzymatic activity not reconstituted in vitro
    • Mechanism of IMC collapse downstream of substrate modification unresolved
  2. 2020 High

    To resolve whether TgDHHC14 and TgDHHC2 act on the same pathway, reciprocal depletion with substrate readouts showed TgDHHC2 (not TgDHHC14) controls membrane association of TgISP1/3 and TgIAP1/2, establishing that the two PATs act sequentially on distinct substrates during IMC sub-compartment formation.

    Evidence Individual conditional disruption of TgDHHC2 and TgDHHC14 with localization readouts of known palmitoylated IMC proteins as substrate proxies

    PMID:32329212

    Open questions at the time
    • The specific substrates acted on by TgDHHC14 remain undefined
    • Stage/ordering of TgDHHC14 action within IMC biogenesis not molecularly mapped
    • No direct enzyme-substrate biochemistry

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
TGDHHC2 (FUNCTIONALLY SEQUENTIAL PAT ACTING ON DISTINCT IMC SUBSTRATES)

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 TgDHHC14 localizes to the inner membrane complex (IMC) of Toxoplasma gondii tachyzoites, and its disruption causes rapid collapse of the IMC in developing daughter cells with dramatic morphological defects, establishing TgDHHC14 as an IMC-resident palmitoyl acyltransferase essential for IMC biogenesis. Conditional disruption (loss-of-function), subcellular localization by imaging, morphological phenotype analysis Cellular microbiology High 32329212
2020 TgDHHC14 and TgDHHC2 act sequentially in IMC sub-compartment formation: TgDHHC2 palmitoylates TgISP1/3 and TgIAP1/2 (which lose membrane association upon TgDHHC2 depletion but are unaffected by TgDHHC14 depletion), indicating that TgDHHC14 acts on a distinct set of IMC substrates at a different stage of IMC biogenesis. Conditional disruption of TgDHHC2 and TgDHHC14 individually, followed by localization assays for known palmitoylated IMC proteins (TgISP1/3, TgIAP1/2) as substrate readouts Cellular microbiology High 32329212

Source papers

Stage 0 corpus · 1 paper · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Two palmitoyl acyltransferases involved sequentially in the biogenesis of the inner membrane complex of Toxoplasma gondii. Cellular microbiology 7 32329212