FRM2

TgFRM2 is a formin that drives actin-dependent apicoplast inheritance during Toxoplasma gondii cell division (PMID:30753127). Its FH1-FH2 domains nucleate polymerization of the normally unstable parasite actin TgACTI in vitro without requiring profilin, making it one of the few known factors capable of initiating assembly of this actin, and they additionally bundle the resulting filaments; profilin (TgPRF) does not assist but instead inhibits FRM2-driven polymerization by sequestering G-actin monomers (PMID:22397711). In the parasite, TgFRM2 localizes to the apical juxtanuclear region, where its disruption abolishes an apicoplast-associated F-actin population and impairs inheritance of this organelle (PMID:30753127). Beyond nucleation, bundling, localization, and the apicoplast-inheritance phenotype, no further mechanistic detail has been characterized in the available corpus.

1. 2012 High

   Whether any factor could initiate polymerization of the intrinsically unstable T. gondii actin was unresolved; this established TgFRM2 as a bona fide nucleator and bundler of TgACTI and clarified profilin's antagonistic role.

   Evidence In vitro actin polymerization assays with purified TgFRM2 FH1-FH2 domains and TgACTI

   PMID:22397711

   Open questions at the time

   • In vitro reconstitution does not establish the cellular context or filament population generated in vivo
   • No structural basis for nucleation or bundling defined
   • Role of full-length TgFRM2 beyond the FH1-FH2 fragment not tested
2. 2019 High

   The cellular function of TgFRM2 was unknown; genetic disruption plus F-actin reporters localized it to the apical juxtanuclear region and tied it to a specific F-actin population required for apicoplast inheritance.

   Evidence Gene disruption combined with F-actin chromobody live imaging and direct fluorescence localization in T. gondii

   PMID:30753127

   Open questions at the time

   • Mechanism linking the FRM2-generated F-actin to physical apicoplast segregation not resolved
   • Regulators recruiting or activating FRM2 at the juxtanuclear region unidentified
   • Whether the in vitro nucleation/bundling activity directly produces the apicoplast-associated actin population not demonstrated

• How TgFRM2 is recruited and regulated at the apical juxtanuclear region, and how the F-actin it generates mechanically drives apicoplast segregation, remain open.
• No upstream regulators or recruitment mechanism identified
• No structural model of the FRM2-actin interaction
• Direct connection between in vitro bundling activity and organelle inheritance untested