FTS

TgFTS (Fused Toes homolog) is a component of a partially conserved FHF-like trafficking adaptor complex in Toxoplasma gondii, assembling with TgHOOK and the coccidian-specific protein HIP (HOOK interacting partner) to control apical positioning and regulated exocytosis of micronemes (PMID:37093045, PMID:37933960). FTS and HOOK colocalize at the parasite apical tip, where FTS is required for rapid apical trafficking of micronemes as parasites initiate motility (PMID:37933960). Conditional depletion of FTS impairs microneme secretion and consequently blocks host cell attachment, motility, invasion, and egress, establishing this complex as essential for the secretory organelle exocytosis that underlies the lytic cycle (PMID:37093045, PMID:37933960). The complex operates downstream of Ca2+-regulated kinase signaling: HOOK is phosphorylated in a CDPK1-dependent manner, placing the FTS-HOOK complex under control of CDPK1 during microneme exocytosis (PMID:37933960).

1. 2023 High

   It was unknown how micronemes are positioned and trafficked to the apical tip for regulated secretion; identifying FTS as part of an FHF-like complex with HOOK and HIP established a conserved adaptor machinery governing apical microneme exocytosis.

   Evidence Co-immunoprecipitation and complex characterization with conditional depletion and microneme secretion/motility/invasion/egress readouts in T. gondii

   PMID:37093045 PMID:37933960

   Open questions at the time

   • Molecular architecture of the FTS-HOOK-HIP complex is not resolved structurally
   • The direct cargo-adaptor or motor linkage mediating trafficking is not defined
2. 2023 High

   Whether FTS was functionally required rather than merely a complex member was open; conditional loss-of-function showed FTS is essential for apical microneme positioning and secretion, and thus for the attach-invade-egress lytic cycle.

   Evidence Conditional depletion with microneme secretion, invasion, egress, and motility assays in T. gondii

   PMID:37093045 PMID:37933960

   Open questions at the time

   • Whether FTS loss affects other secretory organelles (e.g. rhoptries, dense granules) is not addressed
   • The specific step in exocytosis blocked by FTS loss is not pinpointed
3. 2023 Medium

   The subcellular site and dynamic role of FTS were unclear; imaging placed FTS and HOOK at the apical tip and demonstrated FTS is required for rapid apical microneme trafficking during motility initiation.

   Evidence Fluorescence co-localization and live imaging of microneme trafficking upon conditional depletion in T. gondii

   PMID:37933960

   Open questions at the time

   • Single-lab observation for the trafficking dynamics
   • The cytoskeletal or motor track along which trafficking occurs is not identified
4. 2023 Medium

   How the FTS complex is coupled to secretory signaling was unknown; CDPK1-dependent phosphorylation of HOOK placed the FTS-HOOK complex downstream of Ca2+-regulated kinase signaling in microneme exocytosis.

   Evidence Sub-minute phosphoproteomics with bio-orthogonal CDPK1 substrate labeling in T. gondii

   PMID:37933960

   Open questions at the time

   • FTS itself was not shown to be directly phosphorylated; pathway placement of FTS is inferred via HOOK
   • The functional consequence of HOOK phosphorylation on complex activity is not established

• The structural organization of the FTS-HOOK-HIP complex and the direct molecular link between this adaptor and the trafficking/exocytic machinery remain undefined.
• No structural model of the complex
• No identified motor or cargo receptor bridging FTS to microneme transport
• Role of FTS outside microneme trafficking unexplored