Giant FAZ10 is required for flagellum attachment zone stabilization and furrow positioning in Trypanosoma brucei

Moreira, B. P. , Da Fonseca, C. K. , Hammarton, T. C. and Baqui, M. M.A. (2017) Giant FAZ10 is required for flagellum attachment zone stabilization and furrow positioning in Trypanosoma brucei. Journal of Cell Science, 130(6), pp. 1179-1193. (doi: 10.1242/jcs.194308) (PMID:28193733) (PMCID:PMC5358337)

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Abstract

The flagellum and flagellum attachment zone (FAZ) are important cytoskeletal structures in trypanosomatids, being required for motility, cell division and cell morphogenesis. Trypanosomatid cytoskeletons contain abundant high molecular mass proteins (HMMPs), but many of their biological functions are still unclear. Here, we report the characterization of the giant FAZ protein, FAZ10, in Trypanosoma brucei, which, using immunoelectron microscopy, we show localizes to the intermembrane staples in the FAZ intracellular domain. Our data show that FAZ10 is a giant cytoskeletal protein essential for normal growth and morphology in both procyclic and bloodstream parasite life cycle stages, with its depletion leading to defects in cell morphogenesis, flagellum attachment, and kinetoplast and nucleus positioning. We show that the flagellum attachment defects are probably brought about by reduced tethering of the proximal domain of the paraflagellar rod to the FAZ filament. Further, FAZ10 depletion also reduces abundance of FAZ flagellum domain protein, ClpGM6. Moreover, ablation of FAZ10 impaired the timing and placement of the cleavage furrow during cytokinesis, resulting in premature or asymmetrical cell division.

Item Type:Articles
Additional Information:This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/19547-1 to M.M.A.B.), by Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (to M.M.A.B.) and by the Medical Research Council (GO900239 to T.C.H.). B.P.M. received a doctoral fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (2012/22129-2) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–PDSE (BEX 6508/15-4).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hammarton, Dr Tansy
Authors: Moreira, B. P., Da Fonseca, C. K., Hammarton, T. C., and Baqui, M. M.A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Cell Science
Publisher:Company of Biologists
ISSN:0021-9533
ISSN (Online):1477-9137
Published Online:13 February 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Journal of Cell Science 130(6):1179-1193
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
493121The NDR kinase pathway in Trypanosoma bruceiTansy HammartonMedical Research Council (MRC)G0900239III - PARASITOLOGY