IMC1g

PF3D7_0525800 (IMC1g) is an alveolin-family inner membrane complex (IMC) protein that anchors the glideosome to the subpellicular network and is required for Plasmodium survival and motility across life-cycle stages (PMID:37712738, PMID:39576115). In P. falciparum, IMC1g localizes to the IMC during asexual blood-stage development and is essential for parasite survival, with conditional knockdown pinpointing a defect post-invasion, indicating a role in merozoite intracellular survival rather than in the invasion event itself (PMID:37712738). IMC targeting is directed by intrinsic sequence features: its IMCp/alveolin domain carries unique signatures for compartment-specific localization, and this targeting does not depend on interaction with IMC1c (PMID:41019501); in the P. berghei ortholog, the IMCp domain is required for IMC targeting while the C-terminus and palmitoylation sites contribute to full targeting efficiency (PMID:39576115). IMC1g interacts with IMC1c, a component of the PHIL1 complex, through a conserved 'EKI(V)V(I)EVP' sub-repeat motif (PMID:39576115). The protein's function is evolutionarily conserved, as P. vivax IMC1g functionally complements the P. berghei ortholog (PMID:39576115). Species-specific phenotypes diverge in scope: in P. berghei, knockdown disrupts schizogony, male gametogenesis, ookinete development and motility, and mosquito midgut invasion (PMID:39576115), whereas in P. falciparum the characterized essentiality is in the asexual blood stage (PMID:37712738).

1. 2023 High

   Establishing whether IMC1g is functionally required at all, and at which step, distinguished it as an essential factor for intracellular survival rather than for invasion.

   Evidence conditional knockdown with post-invasion survival phenotyping in P. falciparum asexual blood stages

   PMID:37712738

   Open questions at the time

   • the molecular cause of the post-invasion survival defect is not defined
   • whether the phenotype reflects IMC structural collapse or a downstream signaling failure is unresolved
2. 2023 Medium

   Determining subcellular localization placed IMC1g at the inner membrane complex, connecting its essentiality to IMC biology.

   Evidence fluorescence microscopy localization comparing the four asexual-stage alveolins in P. falciparum

   PMID:37712738

   Open questions at the time

   • localization within IMC sub-domains not resolved
   • dynamics across the asexual cycle not fully mapped
3. 2024 Medium

   Mapping IMC targeting determinants in the ortholog showed the IMCp domain drives IMC localization, with C-terminal and palmitoylation contributions to efficiency.

   Evidence domain deletion and palmitoylation-site mutagenesis with fluorescence localization in P. berghei across schizonts, activated gametocytes, and ookinetes

   PMID:39576115

   Open questions at the time

   • identity of the palmitoyl transferase acting on IMC1g not established
   • which IMC binding partner reads the IMCp domain not identified
4. 2024 Medium

   Identifying the IMC1c interaction and its motif dependence defined a molecular link connecting IMC1g to the PHIL1 complex.

   Evidence pairwise yeast two-hybrid with motif deletion/mutagenesis of the 'EKI(V)V(I)EVP' sub-repeat in P. berghei

   PMID:39576115

   Open questions at the time

   • interaction not confirmed by orthogonal in-cell or reciprocal co-IP methods
   • stoichiometry and direct-vs-bridged nature of the IMC1c contact unknown
5. 2024 High

   Multi-stage knockdown phenotyping assigned IMC1g a role anchoring the glideosome to the subpellicular network across the parasite life cycle.

   Evidence conditional knockdown with phenotyping of schizogony, male gametogenesis, ookinete development and motility, and midgut invasion in P. berghei

   PMID:39576115

   Open questions at the time

   • direct biochemical demonstration of glideosome tethering not shown
   • whether motility defects are structural or regulatory is unresolved
6. 2024 Medium

   Cross-species complementation demonstrated that IMC1g function is evolutionarily conserved.

   Evidence heterologous expression of P. vivax IMC1g rescuing P. berghei imc1g knockdown

   PMID:39576115

   Open questions at the time

   • degree of functional rescue across all life-cycle stages not fully quantified
   • conservation of the IMC1c interaction motif not directly tested for the P. vivax protein
7. 2025 Medium

   Testing whether IMC1c binding was needed for IMC localization separated targeting from complex assembly and revealed IMC1g-intrinsic localization signatures.

   Evidence domain deletion/swap experiments with fluorescence localization readout in P. falciparum

   PMID:41019501

   Open questions at the time

   • the specific sequence signatures conferring compartment-specific targeting are not defined at residue level
   • the receptor or scaffold recognizing these signatures is unidentified

• How IMC1g mechanistically bridges the glideosome and subpellicular network, and the molecular basis of its post-invasion essentiality in P. falciparum, remain unresolved.
• no structural model of IMC1g or its IMC1c interface
• no direct biochemical demonstration of glideosome tethering
• the full IMC1g interactome beyond IMC1c is uncharacterized