title: Modulation of flagellum attachment zone protein FLAM3 and regulation of the cell shape in Trypanosoma brucei life cycle transitions.
abstract: The cell shape of Trypanosoma brucei is influenced by flagellum-to-cell-body attachment through a specialised structure - the flagellum attachment zone (FAZ). T. brucei exhibits numerous morphological forms during its life cycle and, at each stage, the FAZ length varies. We have analysed FLAM3, a large protein that localises to the FAZ region within the old and new flagellum. Ablation of FLAM3 expression causes a reduction in FAZ length; however, this has remarkably different consequences in the tsetse procyclic form versus the mammalian bloodstream form. In procyclic form cells FLAM3 RNAi results in the transition to an epimastigote-like shape, whereas in bloodstream form cells a severe cytokinesis defect associated with flagellum detachment is observed. Moreover, we demonstrate that the amount of FLAM3 and its localisation is dependent on ClpGM6 expression and vice versa. This evidence demonstrates that FAZ is a key regulator of trypanosome shape, with experimental perturbations being life cycle form dependent. An evolutionary cell biology explanation suggests that these differences are a reflection of the division process, the cytoskeleton and intrinsic structural plasticity of particular life cycle forms.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Jack D
authors.initials: JD
authors.lastname: Sunter
authors.affiliation: Faculty of Sciences, University of South Bohemia, České Budějovice (Budweis) 37005, Czech Republic.
authors.forename: Corinna
authors.initials: C
authors.lastname: Benz
authors.affiliation: Faculty of Health and Medicine, Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Andre
authors.affiliation: Faculty of Health and Medicine, Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Whipple
authors.affiliation: Faculty of Health and Medicine, Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: Paul G
authors.initials: PG
authors.lastname: McKean
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK keith.gull@path.ox.ac.uk m.ginger@lancaster.ac.uk jula@paru.cas.cz.
authors.forename: Keith
authors.initials: K
authors.lastname: Gull
authors.affiliation: Faculty of Health and Medicine, Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YQ, UK keith.gull@path.ox.ac.uk m.ginger@lancaster.ac.uk jula@paru.cas.cz.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Ginger
authors.affiliation: Faculty of Sciences, University of South Bohemia, České Budějovice (Budweis) 37005, Czech Republic Institute of Parasitology, Biology Centre, Czech Academy of Sciences, České Budějovice (Budweis) 37005, Czech Republic Canadian Institute for Advanced Research, Toronto, Ontario, Canada M5G 1Z8 keith.gull@path.ox.ac.uk m.ginger@lancaster.ac.uk jula@paru.cas.cz.
authors.forename: Julius
authors.initials: J
authors.lastname: Lukeš
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000235:genetics*; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D048749:Cytokinesis / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics* / Q000378:metabolism; D005407:Flagella / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008018:Life Cycle Stages / Q000235:genetics*; D008870:Microtubules / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000254:growth & development
chemical_list: D015800:Protozoan Proteins
keywords: Flagellum attachment zone; Morphogenesis; Trypanosomes