IMC1l

PF3D7_1417000 (IMC1l) is an alveolin of Plasmodium falciparum that functions as a candidate membrane-cytoskeleton linker coupling the inner membrane complex (IMC) to the parasite gliding apparatus (PMID:30599160). Biochemical pulldown assays established that IMC1l directly binds both actin and myosin, with the two cytoskeletal proteins competing for the same site, and that it simultaneously binds actin together with either cholesterol or PIP2, positioning it to bridge the IMC lipid bilayer to the actin-myosin machinery (PMID:30599160). IMC1l also binds calcium directly, and calcium enhances its interaction with actin, indicating a calcium-dependent regulation of this membrane-cytoskeleton coupling (PMID:30599160). Consistent with this bridging role, IMC1l is expressed in vivo and localizes to the IMC (PMID:30599160). Beyond these binding and localization observations, no in vivo functional, genetic, or structural characterization of IMC1l has been established in the available corpus.

1. 2018 Medium

   To define whether IMC1l could physically link the IMC to the gliding machinery, its direct binding partners were tested, revealing simultaneous protein-protein and protein-lipid interactions consistent with a membrane-cytoskeleton bridge.

   Evidence Biochemical binding/pulldown assays, in silico structural analysis, and calcium-binding assays in P. falciparum

   PMID:30599160

   Open questions at the time

   • No reciprocal Co-IP or in vivo functional rescue confirms the interactions
   • Stoichiometry and physiological relevance of actin/myosin competition unresolved
   • No structural model of the actin/lipid/calcium binding sites experimentally determined
2. 2018 Low

   To place IMC1l in a subcellular context, its expression and localization were examined, showing IMC residence consistent with the proposed anchoring role.

   Evidence In vivo expression analysis and subcellular localization in P. falciparum

   PMID:30599160

   Open questions at the time

   • Localization reported in a single study without independent replication or detailed imaging method
   • No functional rescue or knockdown links localization to the anchoring function
   • Stage-specific expression dynamics not characterized

• Whether IMC1l is genetically required for gliding motility, IMC integrity, or parasite invasion, and how its calcium-dependent actin binding is regulated in vivo, remain unknown.
• No loss-of-function phenotype established
• No demonstration that binding partners engage IMC1l in living parasites
• No mechanistic link between calcium binding and gliding motility in vivo