MIC11

TgMIC11 is a soluble apical microneme protein of Toxoplasma gondii that functions in the parasite lytic cycle, undergoing calcium-dependent secretion and proteolytic maturation (PMID:15313131). The 16 kDa protein is matured by two successive cleavages that remove an internal propeptide, yielding an alpha-chain and beta-chain held together by a single disulfide bond (PMID:15313131). Functionally, MIC11 is essential for PLP1-dependent permeabilization of the host cell membrane during parasite egress: its deletion causes severe defects in membrane rupture and egress, and it acts through a direct physical association with PLP1, with functional motifs mapped by scanning mutagenesis (PMID:41935076). The merozoite-specific paralogue MIC22 complements MIC11 loss, indicating a conserved egress mechanism across the feline-restricted stages (PMID:41935076).

1. 2004 High

   Establishing whether MIC11 is a genuine microneme protein and how it is structurally organized defined it as a novel secretory protein processed into a disulfide-linked heterodimer.

   Evidence Biochemical processing assays, structural characterization, and dual-staining immunofluorescence in T. gondii

   PMID:15313131

   Open questions at the time

   • The protease(s) responsible for the two maturation cleavages were not identified
   • The functional consequence of the alpha/beta heterodimer architecture was not defined
2. 2004 High

   Determining the subcellular localization and secretion behavior placed MIC11 at the apical micronemes and showed calcium-dependent release, consistent with an early host-interaction role.

   Evidence Dual-staining immunofluorescence and calcium-dependent secretion assay in T. gondii

   PMID:15313131

   Open questions at the time

   • No molecular binding partner or substrate was identified at this stage
   • The specific step of the lytic cycle requiring MIC11 was not established
3. 2026 High

   Assigning a loss-of-function phenotype and a binding partner revealed MIC11 as an essential effector of PLP1-mediated host membrane permeabilization during egress rather than solely an invasion factor.

   Evidence CRISPR fitness screen, gene deletion, scanning mutagenesis, and MIC11–PLP1 interaction analyses in T. gondii

   PMID:41935076

   Open questions at the time

   • The structural basis of the MIC11–PLP1 association is not resolved
   • How MIC11 mechanistically potentiates PLP1 membrane rupture is not defined
   • Whether the disulfide-linked mature form is the species that engages PLP1 is not established
4. 2026 Medium

   Testing paralogue redundancy showed the merozoite-specific MIC22 can substitute for MIC11, indicating the egress function is conserved across feline-restricted stages.

   Evidence Genetic complementation assay in which MIC22 rescues the MIC11 deletion phenotype in T. gondii

   PMID:41935076

   Open questions at the time

   • Detail limited to abstract-level reporting
   • Whether MIC22 engages PLP1 through the same motifs as MIC11 is not shown
   • The physiological role of MIC22 in the natural merozoite stage was not directly tested

• The precise molecular mechanism by which MIC11 promotes PLP1-driven membrane permeabilization, and the structural determinants of the interaction, remain unresolved.
• No structural model of the MIC11–PLP1 complex
• Identity of the maturation proteases unknown
• Whether MIC11 acts before, during, or after PLP1 membrane insertion is undefined