IMC1b

IMC1b (PF3D7_1141900), characterized through its P. berghei ortholog, is a membrane skeletal component of the ookinete pellicle that localizes exclusively to the subpellicular network and provides mechanical strength, normal cell shape, gliding motility, and mosquito midgut infectivity, as demonstrated by GFP-tagging and targeted gene disruption (PMID:18650444). Genetic epistasis with IMC1h shows that IMC1b's contribution to gliding motility is separable from its role in maintaining ookinete morphology: double knockout worsens tensile strength, motility, and infectivity defects beyond either single mutant without further altering cell shape (PMID:21098480). IMC1b is a phosphorylation target of the cGMP-dependent protein kinase PKG in gliding ookinetes, placing it downstream of the PKG signalling pathway that controls motility (PMID:24594931), and it co-purifies with the FBXO1 ubiquitin-ligase complex within the subpellicular filamentous layer beneath the inner membrane complex (PMID:36898988). No direct enzymatic activity or atomic-resolution structure of IMC1b has been established in the available corpus.

1. 2008 High

   Established that IMC1b is a pellicle-associated membrane skeletal protein required for ookinete integrity, answering whether the gene has a structural role in the invasive-stage cytoskeleton.

   Evidence GFP-tagging for localization plus targeted gene knockout with morphology, tensile strength, gliding motility, and mosquito infectivity readouts in P. berghei

   PMID:18650444

   Open questions at the time

   • Molecular partners within the subpellicular network not defined
   • No structural model of how IMC1b confers mechanical strength
   • Function assessed only in P. berghei ookinetes, not in P. falciparum
2. 2010 High

   Separated IMC1b's role in gliding motility from its role in cell shape, resolving whether its functions are mechanistically coupled.

   Evidence IMC1b/IMC1h double null mutants generated by targeted disruption with tensile strength, motility, and infectivity assays in P. berghei

   PMID:21098480

   Open questions at the time

   • Molecular basis for the motility-versus-morphology separation unknown
   • How IMC1b and IMC1h partition within the same network not resolved
3. 2014 Medium

   Placed IMC1b downstream of PKG signalling by identifying it as a phosphorylation target in gliding ookinetes, linking the skeletal protein to a motility-controlling kinase pathway.

   Evidence Quantitative phosphoproteomics of P. berghei ookinetes comparing PKG inhibitor-treated versus untreated parasites

   PMID:24594931

   Open questions at the time

   • Site-specific mutagenesis of IMC1b phosphosites not performed
   • Functional consequence of IMC1b phosphorylation on motility not demonstrated
   • Whether PKG phosphorylates IMC1b directly or indirectly unknown
4. 2023 Low

   Associated IMC1b with the FBXO1 pellicular protein network, raising the possibility of ubiquitin-ligase-linked regulation at the subpellicular layer.

   Evidence Immunoprecipitation of FBXO1-HA followed by mass spectrometry in P. berghei ookinetes 12 h post-activation

   PMID:36898988

   Open questions at the time

   • Single Co-IP/MS from one biological replicate without reciprocal pulldown
   • No functional validation of the FBXO1-IMC1b association specific to IMC1b
   • Whether IMC1b is a ubiquitination substrate of the FBXO1 complex untested

• How IMC1b physically integrates into the subpellicular network and whether its phosphorylation or FBXO1 association mechanistically controls gliding motility remains unresolved.
• No atomic-resolution structure or defined biochemical activity
• Direct binding partners in the subpellicular network not mapped
• No characterization of IMC1b in P. falciparum itself