STX21

TgStx21 is a syntaxin-family SNARE that functions as part of an unconventional SNARE complex with TgStx1 and TgStx20 to drive vesicular fusion at the plasma membrane of Toxoplasma gondii (PMID:36972314). This complex localizes specifically to the apical annuli, subapical annular structures embedded in the inner membrane complex, which serve as sites of dense granule vesicle fusion and exocytosis (PMID:38270431). Through this activity TgStx21 is required for exocytosis of surface proteins and post-invasion secretion of dense granule cargo, and perturbation of secretion at the apical annuli strongly impairs parasite growth (PMID:36972314, PMID:38270431). Beyond its role in this fusion complex and its apical annuli localization, no further mechanistic detail on TgStx21 has been characterized in the available corpus.

1. 2023 Medium

   It was unknown how vesicular fusion at the Toxoplasma plasma membrane is executed; identifying an unconventional SNARE complex of TgStx1, TgStx20, and TgStx21 established the molecular machinery mediating fusion and its requirement for surface protein exocytosis.

   Evidence Genetic and biochemical SNARE complex composition analysis with loss-of-function functional studies in T. gondii

   PMID:36972314

   Open questions at the time

   • Single lab study without independent replication
   • Stoichiometry and structural arrangement of the TgStx1/TgStx20/TgStx21 complex not resolved
   • The specific SNARE role of TgStx21 within the complex versus its partners not separated
2. 2024 Medium

   It was unclear where in the parasite this SNARE-mediated fusion occurs; localizing TgStx21 to the apical annuli and linking these sites to dense granule fusion established the apical annuli as functional exocytic hubs whose perturbation impairs growth.

   Evidence Fluorescence localization of SNARE proteins at apical annuli combined with functional perturbation and growth phenotype readout

   PMID:38270431

   Open questions at the time

   • Molecular mechanism recruiting TgStx21 to the apical annuli unknown
   • Identity of the vesicular (R-)SNARE partner completing fusion not established
   • Full repertoire of cargo secreted at apical annuli not defined

• How TgStx21 is targeted to the apical annuli and how the complex is regulated to control the timing of dense granule and surface protein secretion remains unresolved.
• No structural model of the SNARE complex
• Regulatory factors controlling fusion timing unidentified
• Cognate R-SNARE / regulatory proteins not identified