title: Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA as Rab-effector kinases in malaria parasites.
abstract: BACKGROUND
  The pathology causing stages of the human malaria parasite Plasmodium falciparum reside within red blood cells that are devoid of any regulated transport system. The parasite, therefore, is entirely responsible for mediating vesicular transport within itself and in the infected erythrocyte cytoplasm, and it does so in part via its family of 11 Rab GTPases. Putative functions have been ascribed to Plasmodium Rabs due to their homology with Rabs of yeast, particularly with Saccharomyces that has an equivalent number of rab/ypt genes and where analyses of Ypt function is well characterized.
  
  
  RESULTS
  Rabs are important regulators of vesicular traffic due to their capacity to recruit specific effectors. In order to identify P. falciparum Rab (PfRab) effectors, we first built a Ypt-interactome by exploiting genetic and physical binding data available at the Saccharomyces genome database (SGD). We then constructed a PfRab-interactome using putative parasite Rab-effectors identified by homology to Ypt-effectors. We demonstrate its potential by wet-bench testing three predictions; that casein kinase-1 (PfCK1) is a specific Rab5B interacting protein and that the catalytic subunit of cAMP-dependent protein kinase A (PfPKA-C) is a PfRab5A and PfRab7 effector.
  
  
  CONCLUSIONS
  The establishment of a shared set of physical Ypt/PfRab-effector proteins sheds light on a core set Plasmodium Rab-interactants shared with yeast. The PfRab-interactome should benefit vesicular trafficking studies in malaria parasites. The recruitment of PfCK1 to PfRab5B+ and PfPKA-C to PfRab5A+ and PfRab7+ vesicles, respectively, suggests that PfRab-recruited kinases potentially play a role in early and late endosome function in malaria parasites.
authors.affiliation: Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS (UMR 8104), 75014 Paris, France.
authors.forename: Fathia Ben
authors.initials: FB
authors.lastname: Rached
authors.forename: Carinne
authors.initials: C
authors.lastname: Ndjembo-Ezougou
authors.forename: Syama
authors.initials: S
authors.lastname: Chandran
authors.forename: Hana
authors.initials: H
authors.lastname: Talabani
authors.forename: Hélène
authors.initials: H
authors.lastname: Yera
authors.forename: Vrushali
authors.initials: V
authors.lastname: Dandavate
authors.forename: Pierre
authors.initials: P
authors.lastname: Bourdoncle
authors.forename: Markus
authors.initials: M
authors.lastname: Meissner
authors.forename: Utpal
authors.initials: U
authors.lastname: Tatu
authors.forename: Gordon
authors.initials: G
authors.lastname: Langsley
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D005810:Multigene Family; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D020691:rab GTP-Binding Proteins