scholarly journals Evidence for an interplay between cell cycle progression and the initiation of differentiation between life cycle forms of African trypanosomes.

1994 ◽  
Vol 125 (5) ◽  
pp. 1147-1156 ◽  
Author(s):  
K R Matthews ◽  
K Gull
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Blood Stream ◽  
Tsetse Fly ◽  
Mammalian Host ◽  
Cycle Progression ◽  
African Trypanosomes ◽  
Host Blood ◽  
Proliferative Cell ◽  
Differentiation Model

Successful transmission of the African trypanosome between the mammalian host blood-stream and the tsetse fly vector involves dramatic alterations in the parasite's morphology and biochemistry. This differentiation through to the tsetse midgut procyclic form is accompanied by re-entry into a proliferative cell cycle. Using a synchronous differentiation model and a variety of markers diagnostic for progress through both differentiation and the cell cycle, we have investigated the interplay between these two processes. Our results implicate a relationship between the trypanosome cell cycle position and the perception of the differentiation signal and demonstrate that irreversible commitment to the differentiation occurs rapidly after induction. Furthermore, we show that re-entry into the cell cycle in the differentiating population is synchronous, and that once initiated, progress through the differentiation pathway can be uncoupled from progress through the cell cycle.

scholarly journals Stage-specific Requirement of a Mitogen-activated Protein Kinase by Trypanosoma brucei

2002 ◽  
Vol 13 (11) ◽  
pp. 3787-3799 ◽  
Author(s):  
Ingrid B. Müller ◽  
Debora Domenicali-Pfister ◽  
Isabel Roditi ◽  
Erik Vassella
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Phosphorylation Site ◽  
Tsetse Fly ◽  
Mitogen Activated Protein Kinase ◽  
Mammalian Host ◽  
Null Mutant ◽  
African Trypanosomes ◽  
Mitogen Activated Protein

In cycling between the mammalian host and the tsetse fly vector, African trypanosomes undergo adaptive differentiation steps that are coupled to growth control. The signaling pathways underlying these cellular processes are largely unknown. Mitogen-activated protein kinases (MAPKs) are known mediators of growth and differentiation in other eukaryotic organisms. To establish the function of a MAPK homologue, TbMAPK2, in T. brucei, a null mutant was constructed. Bloodstream forms of aΔmapk2/Δmapk2 clone were able to grow normally and exhibited no detectable phenotype. When these cells were triggered to differentiate in vitro, however, they developed to the procyclic (fly midgut) form with delayed kinetics and subsequently underwent cell cycle arrest. Introduction of an ectopic copy of theTbMAPK2 gene into the null mutant restored its ability to differentiate and to divide. In contrast, a TbMAPK2mutant, in which the T190 and Y192 residues of the activating phosphorylation site were replaced by A and F, was unable to restore the growth and differentiation phenotypes. Analysis of the DNA content and the nucleus/kinetoplast configuration of individual cells showed that the null mutant was arrested in all phases of the cell cycle and that 25–30% of the cells had failed to segregate their nucleus and kinetoplast correctly. This implies that cell cycle progression by the procyclic form depends on a constitutive stimulus exerted by the signaling cascade operating through TbMAPK2.

scholarly journals Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

Development ◽  
2011 ◽  
Vol 138 (11) ◽  
pp. 2223-2234 ◽  
Author(s):  
P. M. Fox ◽  
V. E. Vought ◽  
M. Hanazawa ◽  
M.-H. Lee ◽  
E. M. Maine ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression ◽  
C Elegans ◽  
Proliferative Cell

Maintaining the protective variant surface glycoprotein coat of African trypanosomes

2005 ◽  
Vol 33 (5) ◽  
pp. 981-982 ◽  
Author(s):  
G. Rudenko
Keyword(s):  
Cell Cycle ◽  
Trypanosoma Brucei ◽  
Chronic Infection ◽  
Cell Cycle Progression ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Cycle Progression ◽  
African Trypanosomes ◽  
Immune Attack ◽  
Protective Variant

The African trypanosome Trypanosoma brucei has a precarious existence as an extracellular parasite of the mammalian bloodstream, where it is faced with continuous immune attack. Key to survival is a dense VSG (variant surface glycoprotein) coat, which is repeatedly switched during the course of a chronic infection. New data demonstrate a link between VSG synthesis and cell cycle progression, indicating that VSG is monitored during the trypanosome cell cycle.

scholarly journals Single-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Emma M. Briggs ◽  
Federico Rojas ◽  
Richard McCulloch ◽  
Keith R. Matthews ◽  
Thomas D. Otto
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Trypanosoma Brucei ◽  
Cell Cycle Progression ◽  
Expression Patterns ◽  
Tsetse Fly ◽  
Cycle Progression ◽  
Progressive Development ◽  
Asynchronous Development

AbstractDevelopmental steps in the trypanosome life-cycle involve transition between replicative and non-replicative forms specialised for survival in, and transmission between, mammalian and tsetse fly hosts. Here, using oligopeptide-induced differentiation in vitro, we model the progressive development of replicative ‘slender’ to transmissible ‘stumpy’ bloodstream form Trypanosoma brucei and capture the transcriptomes of 8,599 parasites using single cell transcriptomics (scRNA-seq). Using this framework, we detail the relative order of biological events during asynchronous development, profile dynamic gene expression patterns and identify putative regulators. We additionally map the cell cycle of proliferating parasites and position stumpy cell-cycle exit at early G1 before progression to a distinct G0 state. A null mutant for one transiently elevated developmental regulator, ZC3H20 is further analysed by scRNA-seq, identifying its point of failure in the developmental atlas. This approach provides a paradigm for the dissection of differentiation events in parasites, relevant to diverse transitions in pathogen biology.

scholarly journals Essential Roles for GPI-anchored Proteins in African Trypanosomes Revealed Using Mutants Deficient in GPI8

2003 ◽  
Vol 14 (3) ◽  
pp. 1182-1194 ◽  
Author(s):  
Simon Lillico ◽  
Mark C. Field ◽  
Pat Blundell ◽  
Graham H. Coombs ◽  
Jeremy C. Mottram
Keyword(s):  
Trypanosoma Brucei ◽  
Cell Cycle Progression ◽  
Tsetse Fly ◽  
Bloodstream Form ◽  
Surface Glycoprotein ◽  
Surface Coat ◽  
Immune Challenge ◽  
Gene Encoding ◽  
Cycle Progression ◽  
African Trypanosomes

The survival of Trypanosoma brucei, the causative agent of Sleeping Sickness and Nagana, is facilitated by the expression of a dense surface coat of glycosylphosphatidylinositol (GPI)-anchored proteins in both its mammalian and tsetse fly hosts. We have characterized T. brucei GPI8, the gene encoding the catalytic subunit of the GPI:protein transamidase complex that adds preformed GPI anchors onto nascent polypeptides. Deletion ofGPI8 (to give Δgpi8) resulted in the absence of GPI-anchored proteins from the cell surface of procyclic form trypanosomes and accumulation of a pool of non–protein-linked GPI molecules, some of which are surface located. Procyclic Δgpi8, while viable in culture, were unable to establish infections in the tsetse midgut, confirming that GPI-anchored proteins are essential for insect-parasite interactions. Applying specific inducible GPI8 RNAi with bloodstream form parasites resulted in accumulation of unanchored variant surface glycoprotein and cell death with a defined multinuclear, multikinetoplast, and multiflagellar phenotype indicative of a block in cytokinesis. These data show that GPI-anchored proteins are essential for the viability of bloodstream form trypanosomes even in the absence of immune challenge and imply that GPI8 is important for proper cell cycle progression.

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