MyoF

MyoF (PF3D7_1329100) is a myosin motor of Plasmodium falciparum that supports asexual blood-stage replication through a role in intracellular membrane trafficking (PMID:42141018). Biochemical and structural analyses establish it as a plus-end-directed, processive motor whose long neck region binds up to six copies of the calmodulin homologue PfCaM, consistent with an early observation that the gene encodes IQ light-chain-binding motifs (PMID:42141018, PMID:15754360). Its tail carries WD40 and Rab-like domains not found in other eukaryotic myosin classes, and it associates with vesicle-trafficking proteins including the vesicle marker PfRab18 (PMID:42141018). MyoF localises to a perinuclear membrane compartment and is present at the Kelch13 endocytic compartment (PMID:42141018, PMID:38039338). Conditional glmS knockdown impairs asexual growth, and gene deletion attempts have been unsuccessful, together indicating an essential function during the asexual cycle (PMID:42141018, PMID:31283102). Beyond these findings, the substrates transported by MyoF and the mechanism by which its motor and trafficking domains are coordinated have not been characterized in the available corpus.

1. 2005 Low

   Before any functional characterization, it was unknown whether PF3D7_1329100 was expressed during and structured for a role in blood-stage biology; transcript profiling and sequence analysis placed it as a blood-stage myosin with light-chain-binding capacity.

   Evidence RT-PCR expression profiling and sequence/phylogenetic analysis in P. falciparum

   PMID:15754360

   Open questions at the time

   • No protein-level or functional assay
   • IQ motif light-chain identity not established
2. 2016 Low

   It was unclear whether MyoF participates in a conserved apicomplexan interaction network; structural and complementation work in Toxoplasma gondii implicated a conserved ARO-binding interaction that likely extends to P. falciparum MyoF.

   Evidence Co-immunoprecipitation, crystallography, and cross-species complementation in T. gondii with P. falciparum ARO

   PMID:26769898

   Open questions at the time

   • P. falciparum MyoF-ARO interaction inferred by conservation, not directly demonstrated
   • Rhoptry association of P. falciparum MyoF not shown directly
3. 2019 Low

   Whether MyoF is required for parasite survival was unknown; failed gene deletion attempts pointed to an essential asexual-stage function.

   Evidence Attempted gene knockout in P. falciparum asexual blood stages

   PMID:31283102

   Open questions at the time

   • Essentiality inferred from failed deletion, not confirmed by conditional depletion in this study
   • Stage-specific requirement not defined
4. 2023 Low

   The subcellular pathway MyoF acts in was undefined; proximity labelling placed it at the Kelch13 endocytic compartment, linking it to hemoglobin uptake machinery.

   Evidence BioID proximity labelling and fluorescence co-localisation in P. falciparum

   PMID:38039338

   Open questions at the time

   • No functional dissection of MyoF at the K13 compartment
   • Contribution to endocytosis not tested
5. 2026 Medium

   The motor properties, domain architecture, localization, and essentiality of MyoF were not directly established; combined biochemical, structural, imaging, and conditional-knockdown work defined it as a plus-end-directed processive PfCaM-binding motor with unique trafficking domains at a perinuclear compartment required for asexual growth.

   Evidence Motility and calmodulin-binding assays, AlphaFold prediction, pull-down/MS, expansion and immunoelectron microscopy, and glmS knockdown in P. falciparum

   PMID:42141018

   Open questions at the time

   • Cargo transported by MyoF not identified
   • Functional role of WD40 and Rab-like tail domains untested
   • PfRab18 interaction not validated reciprocally or functionally
   • Coordination of motor activity with trafficking function unresolved

• It remains unknown what cargo MyoF transports and how its motor activity, PfCaM regulation, and unique tail domains are integrated to drive the trafficking events essential for asexual replication.
• No identified transport substrate
• Mechanistic link between K13-compartment localization and endocytosis untested
• No structure of the full-length motor-tail complex