RDF2

RDF2 (formerly annotated MIC14) is a thrombospondin-related transmembrane protein restricted to the Coccidia class of apicomplexans and paralogous to RDF1, comprising a C-terminal transmembrane domain followed by a short cytoplasmic tail (PMID:35756016). It participates in the rhoptry exocytosis pathway of Toxoplasma gondii: upon conditional knockdown of RDF1, RDF2 is spontaneously upregulated, and this compensatory expression restores rhoptry discharge, establishing that RDF2 can functionally substitute for RDF1 in driving rhoptry secretion (PMID:35756016). Beyond this compensatory role in rhoptry discharge, no further mechanistic detail — including its molecular binding partners, the structural basis of its activity, or its behavior under normal expression conditions — has been characterized in the available corpus.

1. 2022 Medium

   Establishing that RDF2 is a distinct Coccidia-specific protein with a defined membrane topology and a paralogous relationship to RDF1 provided the structural framework for asking whether the two proteins share function.

   Evidence Sequence analysis and immunofluorescence of T. gondii tachyzoites

   PMID:35756016

   Open questions at the time

   • Protein was not detected by immunofluorescence under normal conditions, leaving its native localization unresolved
   • No binding partners or substrates identified
   • No structural model of the thrombospondin-related domain or cytoplasmic tail
2. 2022 Medium

   Testing whether RDF2 has a role in rhoptry secretion showed that it is spontaneously upregulated upon RDF1 knockdown and rescues rhoptry discharge, establishing functional redundancy between the paralogs in the rhoptry exocytosis pathway.

   Evidence Conditional knockdown of RDF1 with RDF2 expression monitoring and rhoptry secretion assays in T. gondii

   PMID:35756016

   Open questions at the time

   • Mechanism by which RDF2 promotes rhoptry discharge is unknown
   • The trigger for compensatory upregulation of RDF2 is uncharacterized
   • Whether RDF2 has a non-redundant function under normal RDF1 expression is unresolved

• The molecular mechanism by which RDF2 acts in rhoptry exocytosis — its interaction partners, the role of its transmembrane and cytoplasmic domains, and its function under native conditions — remains unresolved.
• No molecular partners in the rhoptry discharge machinery identified
• No functional dissection of the transmembrane domain or cytoplasmic tail
• Native expression, localization, and non-redundant role undefined