RDF1

RDF1 (formerly annotated MIC15) is a Coccidia-specific thrombospondin-related transmembrane protein that functions specifically at the host cell invasion step of the Toxoplasma gondii tachyzoite lytic cycle (PMID:35756016). The protein carries a C-terminal transmembrane domain and short cytoplasmic tail and localizes to a diffuse punctate compartment distinct from known subcellular organelles (PMID:35756016). Conditional depletion of RDF1 dramatically reduces invasion while leaving gliding motility, host attachment, replication, and egress intact, and mechanistically this defect maps to impaired rhoptry discharge rather than microneme exocytosis (PMID:35756016). RDF1 is functionally redundant with its paralog RDF2: spontaneous upregulation of RDF2 under constant RDF1 repression reverses the rhoptry secretion defect (PMID:35756016). Beyond these findings, the molecular partners and biochemical mechanism by which RDF1 promotes rhoptry discharge have not been characterized in the available corpus.

1. 2022 Medium

   Establishing where a previously misannotated thrombospondin-related protein resides defined RDF1 as a distinct compartment-associated transmembrane protein rather than a canonical microneme component.

   Evidence Immunofluorescence and domain analysis of T. gondii tachyzoites (re-annotating MIC15 as RDF1)

   PMID:35756016

   Open questions at the time

   • The identity of the punctate compartment is undefined
   • No interacting partners at this compartment identified
   • Domain architecture not functionally dissected
2. 2022 Medium

   Conditional knockdown resolved which stage of the lytic cycle depends on RDF1, isolating its role to host cell invasion rather than motility, attachment, replication, or egress.

   Evidence Inducible knockdown with phenotypic assays across the lytic cycle in T. gondii

   PMID:35756016

   Open questions at the time

   • Does not reveal the molecular event RDF1 controls within invasion
   • Single-lab study without independent replication
3. 2022 Medium

   Organelle-specific secretion assays pinpointed the invasion defect to rhoptry discharge, distinguishing RDF1's role from microneme exocytosis.

   Evidence Conditional knockdown coupled to rhoptry and microneme secretion assays in T. gondii

   PMID:35756016

   Open questions at the time

   • Mechanism linking RDF1 to rhoptry discharge unknown
   • Whether RDF1 acts directly on rhoptry machinery or upstream is unresolved
4. 2022 Medium

   Long-term repression revealed that spontaneous upregulation of the paralog RDF2 rescues the rhoptry secretion defect, establishing functional redundancy between RDF1 and RDF2.

   Evidence Conditional knockdown with long-term culture, RDF2 expression monitoring, and rhoptry secretion rescue in T. gondii

   PMID:35756016

   Open questions at the time

   • Regulatory basis of RDF2 upregulation unknown
   • Whether RDF1 and RDF2 act at the same molecular step or through parallel routes is untested

• The molecular mechanism by which RDF1 promotes rhoptry discharge, its interacting partners, and the identity of its punctate compartment remain unknown.
• No binding partners or substrates identified
• No structural model
• The punctate compartment remains unassigned to a known organelle