Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

Monnerat, S., Almeida Costa, C.I., Forkert, A.C., Benz, C., Hamilton, A., Tetley, L., Burchmore, R. , Novo, C., Mottram, J.C. and Hammarton, T.C. (2013) Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei. PLoS ONE, 8(6), e67327. (doi:10.1371/journal.pone.0067327) (PMID:23805309) (PMCID:PMC3689728)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0067327

Abstract

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tetley, Dr Laurence and Burchmore, Dr Richard and Benz, Dr Corinna and Hammarton, Dr Tansy and Hamilton, Mrs Alana and Mottram, Professor Jeremy
Authors: Monnerat, S., Almeida Costa, C.I., Forkert, A.C., Benz, C., Hamilton, A., Tetley, L., Burchmore, R., Novo, C., Mottram, J.C., and Hammarton, T.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS ONE 8(6):e67327
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
403591Regulation of cytokinesis in trypanosoma bruceiTansy HammartonMedical Research Council (MRC)G120/1001 75480III - PARASITOLOGY
371796The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOME)085349/Z/08/ZIII - PARASITOLOGY
617461Can marine calcifying organisms use proteomic responses to adpat to anthropogenic global change? (ISSF Catalyst Fund)Richard BurchmoreWellcome Trust (WELLCOME)097821/Z/11/ZIII - PARASITOLOGY