FLP

FLP (PF3D7_0806300) is the P. falciparum ferlin-like protein, a member of an ancient eukaryotic ferlin family characterized by multiple tandem C2 domains, a C-terminal transmembrane domain, and FerI/FerB structural motifs, with the C-terminal C2E and C2F domains showing the greatest conservation of putative calcium-binding residues (PMID:20667140). Direct functional evidence derives from the P. berghei ortholog, where genetic depletion causes complete life cycle arrest in the mosquito: mature gametes form normally but remain trapped within the red blood cell, and the egress block is rescued by detergent-mediated membrane lysis, establishing FLP as required for the membrane disruption step of gamete egress (PMID:30597708). Consistent with a role in calcium-dependent exocytosis, HA-tagged FLP localizes to intracellular speckles that relocalize to the cell periphery during gamete maturation (PMID:30597708). No direct functional characterization of the P. falciparum PF3D7_0806300 protein itself has been reported in the available corpus beyond its phylogenetic placement (PMID:20667140); the mechanistic role rests on the P. berghei ortholog.

1. 2010 Low

   Whether apicomplexan parasites possess ferlin-family proteins was unresolved; phylogenetic analysis placed PF3D7_0806300 within an ancient eukaryotic ferlin family, defining its domain architecture and flagging the most conserved calcium-binding modules as candidate functional determinants.

   Evidence Phylogenetic analysis and domain architecture mapping across eukaryotic genomes

   PMID:20667140

   Open questions at the time

   • Computational/phylogenetic only — no direct functional experiment on the P. falciparum protein
   • Calcium binding by the C2E/C2F domains is inferred from sequence, not demonstrated
   • No localization or interaction data for PF3D7_0806300 itself
2. 2019 Medium

   The cellular function of the ferlin-like protein was unknown; conditional depletion of the P. berghei ortholog showed it is required for gamete egress via membrane disruption, and its stage-dependent relocalization to the cell periphery linked it to calcium-dependent exocytosis.

   Evidence Conditional genetic knockout in P. berghei sexual stages with HA-tag fluorescence microscopy, detergent rescue, and mosquito infection assay

   PMID:30597708

   Open questions at the time

   • Shown in the P. berghei ortholog, not directly in P. falciparum PF3D7_0806300
   • Molecular mechanism of membrane disruption and identity of any exocytic cargo or partners undefined
   • Whether the C2 domains bind calcium and drive the peripheral relocalization was not tested

• Whether P. falciparum PF3D7_0806300 performs the egress function established for its P. berghei ortholog, and the molecular basis of its calcium-dependent membrane disruption activity, remain open.
• No direct P. falciparum functional or localization data
• No identified binding partners, complex membership, or exocytic machinery link
• No structural or biochemical demonstration of calcium binding