Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA as Rab-effector kinases in malaria parasites

Rached, F.B., Ndjembo-Ezougou, C., Chandran, S., Talabani, H., Yera, H., Dandavate, V., Bourdoncle, P., Meissner, M. , Tatu, U. and Langsley, G. (2012) Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA as Rab-effector kinases in malaria parasites. Biology of the Cell, 104(1), pp. 34-47. (doi: 10.1111/boc.201100081)

Abstract

Background information 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.

• Item Type: Articles
• Additional Information: The definitive version is available at www3.interscience.wiley.com
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Meissner, Professor Markus
• Authors: Rached, F.B., Ndjembo-Ezougou, C., Chandran, S., Talabani, H., Yera, H., Dandavate, V., Bourdoncle, P., Meissner, M., Tatu, U., and Langsley, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Biology of the Cell
• Publisher: John Wiley & Sons Ltd.
• ISSN: 0248-4900
• Published Online: 06 December 2011
• Copyright Holders: Copyright © 2012 Soçiété Francaise des Microscopies and Société de Biologie Cellulaire de France
• First Published: First published in Biology of the Cell 104(1):34-37
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher