RAB5c

RAB5c (PF3D7_0106800) is one of three Rab5-family GTPases in P. falciparum, and genetic evidence establishes that it carries out a distinct, non-overlapping trafficking function from its sibling RAB5b: the P. berghei ortholog of RAB5c fails to complement loss of RAB5b in asexual blood-stage parasites (PMID:24498355, PMID:27316546). Beyond this functional distinction from RAB5b, the specific molecular activity, substrates, effectors, and individual localization of RAB5c have not been characterized in the available corpus. P. falciparum Rab5 proteins as a group mislocalize upon inhibition of the MEP isoprenoid pathway with fosmidomycin, consistent with a requirement for C-terminal prenylation for membrane recruitment and correlating with food-vacuole morphological defects, but this readout reflects the Rab5 family collectively and does not individually resolve RAB5c (PMID:23223036).

1. 2012 Low

   The question of how P. falciparum Rab5 GTPases achieve their membrane localization was addressed by disrupting the isoprenoid supply, showing that Rab5 proteins depend on prenylation-linked membrane recruitment and are tied to food-vacuole integrity.

   Evidence Fosmidomycin inhibition of the MEP pathway with fluorescence microscopy of Rab5 localization and food-vacuole morphology in P. falciparum

   PMID:23223036

   Open questions at the time

   • The readout implicates the Rab5 family collectively and does not distinguish RAB5c from RAB5a or RAB5b
   • Prenylation of RAB5c was not directly demonstrated
   • No individual localization for RAB5c was established
2. 2014 Medium

   Whether the three Rab5 isotypes are functionally redundant was tested by complementation, establishing that RAB5c cannot substitute for RAB5b and therefore performs a distinct trafficking role.

   Evidence Reverse-genetics complementation/epistasis assay using the P. berghei ortholog in haploid asexual blood-stage parasites

   PMID:24498355

   Open questions at the time

   • A failure-to-complement is a negative result and does not define what RAB5c positively does
   • No substrates, effectors, or cargo identified
   • Result obtained in P. berghei ortholog, not directly in P. falciparum RAB5c
3. 2016 Medium

   The non-redundancy of RAB5c with RAB5b was re-tested in an independent complementation analysis of all Rab5 isotypes, confirming the earlier negative complementation result.

   Evidence Complementation analysis of Rab5 isotypes using the P. berghei ortholog

   PMID:27316546

   Open questions at the time

   • Still a negative complementation result; the specific RAB5c function remains undefined
   • No molecular mechanism, GEF/GAP, or effector identified
   • Findings rest on the P. berghei ortholog

• The specific molecular mechanism, subcellular localization, cargo, and effector partners of RAB5c remain undefined; the corpus establishes only that it is a Rab5-family GTPase with a role distinct from RAB5b.
• No individual localization of RAB5c determined
• No GTPase activity, GEF/GAP, or effector interactions established
• No cargo or vesicle-trafficking route assigned specifically to RAB5c