RAB11b

RAB11b (PF3D7_1340700) is a Rab GTPase of the malaria parasite that functions in vesicular trafficking supporting the biogenesis of pellicular structures across the parasite life cycle (PMID:12657463, PMID:39366980). In P. yoelii ookinetes, the RAB11b ortholog acts as a cargo receptor for subpellicular-microtubule dynein-driven transport: it interacts with the dynein heavy chain DHC3 in a DHC3-dependent manner, and its genetic disruption phenocopies DHC3 deficiency, producing defective apical organelle formation, aberrant ookinete morphology, impaired gliding motility, and failure of mosquito infection (PMID:39366980). Consistent with a role in pellicle biogenesis, the RAB11b ortholog localizes to the inner membrane complex (IMC) in P. yoelii schizonts (PMID:35775739). In P. falciparum schizonts, RAB11b physically associates with the SCF ubiquitin ligase components PfSKP1 and PfFBXO1 alongside IMC-associated proteins, linking ubiquitin-mediated regulation to IMC biogenesis (PMID:40592953), and it co-immunoprecipitates with the artemisinin-resistance protein K13 as part of a K13-associated trafficking network (PMID:32310999). Beyond these interaction and localization findings, the biochemical activity of RAB11b itself — its GTPase cycle, effectors, and direct cargo — has not been characterized in the available corpus.

1. 2003 Low

   Establishing that PF3D7_1340700 is an expressed member of the parasite's Rab GTPase repertoire was the first step in defining it as a candidate trafficking regulator rather than a pseudogene or unexpressed locus.

   Evidence Bioinformatic family identification with RT-PCR transcription testing in P. falciparum-infected erythrocytes

   PMID:12657463

   Open questions at the time

   • No functional or localization data specific to RAB11b
   • GTPase activity and cycle not demonstrated
2. 2020 Low

   Placing RAB11b within the K13 artemisinin-resistance interactome connected it to endocytic/vesicular trafficking machinery in the intra-erythrocytic stage.

   Evidence K13 monoclonal-antibody immunoprecipitation followed by mass spectrometry in gene-edited P. falciparum

   PMID:32310999

   Open questions at the time

   • RAB11b identified among many Rab GTPases with no RAB11b-specific functional follow-up
   • Direct versus indirect association with K13 not resolved
3. 2020 Low

   Demonstrating RAB11b protein expression during the zygote-to-ookinete transition established it as a distinct, stage-specific family member co-expressed with RAB11A rather than a redundant paralog.

   Evidence Western blot and immunofluorescence of endogenous PbRAB11b across the transition time course in P. berghei

   PMID:32463831

   Open questions at the time

   • No direct functional manipulation of RAB11b itself
   • Relationship to RAB11A function not defined
4. 2022 Low

   Localizing the RAB11b ortholog to the inner membrane complex in schizonts assigned it a spatial niche at the developing pellicle, framing a role in pellicle/IMC biogenesis.

   Evidence Immunofluorescence of episomal N-terminal HA-tagged protein co-stained with IMC marker GAP45 in P. yoelii schizonts

   PMID:35775739

   Open questions at the time

   • Localization from episomal overexpression, not endogenous tagging
   • No loss-of-function data for RAB11b in this study
5. 2024 Medium

   Identifying RAB11b as a DHC3-dependent receptor for subpellicular-microtubule dynein cargoes provided the first direct mechanistic function: linking motor-driven transport to apical organelle assembly and ookinete morphogenesis.

   Evidence Co-immunoprecipitation with DHC3 plus conditional knockout with morphology, gliding, apical-organelle, and mosquito-infectivity readouts in P. yoelii

   PMID:39366980

   Open questions at the time

   • Single lab, single study in P. yoelii
   • Specific cargoes transported via RAB11b not identified
   • GTPase-cycle dependence of the receptor function not tested
6. 2025 Low

   Detecting RAB11b in PfSKP1 and PfFBXO1 pull-downs alongside IMC proteins hinted at ubiquitin-ligase regulation of RAB11b-associated IMC biogenesis in the blood stage.

   Evidence Co-immunoprecipitation followed by LC-MS/MS from schizont-stage P. falciparum expressing HA-tagged PfSKP1 and PfFBXO1

   PMID:40592953

   Open questions at the time

   • Single Co-IP/MS with no RAB11b-specific functional follow-up
   • Whether RAB11b is a ubiquitylation substrate of the SCF complex not tested
   • Direct versus indirect association not established

• The intrinsic biochemistry of RAB11b — its GTP/GDP cycle, GEF/GAP regulators, and the identity of cargoes it delivers — remains undefined, as does whether its blood-stage IMC/SCF/K13 associations reflect the same cargo-receptor function seen in ookinetes.
• No reconstitution of RAB11b GTPase or effector binding
• No cargo directly identified
• Cross-stage and cross-species conservation of function untested