Motility and more: the flagellum of Trypanosoma brucei

Langousis, Gerasimos; Hill, Kent L.

doi:10.1038/nrmicro3274

Cited by 155 publications

(180 citation statements)

References 173 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…As the daughter cells move apart, they become oriented such that beating of the extracellular flagella can propel the cells in opposite directions for scission. A mechanical role for the flagella, however, does not exclude the possibility that the flagella could have additional roles, such as serving as a scaffold for transport or polarity signaling (51,60,61).…”

Section: Giardia Uses a Tubulin Reservoir To Support Rapid Mitosis Anmentioning

confidence: 99%

“…Myosin II mutants of Dictyostelium were shown to use ameboid motility to crawl apart for cytokinesis (17). Organisms that lack myosin II and depend on their flagella for motility, such as Trypanosoma brucei and Tetrahymena, also require motility for abscission (50)(51)(52). To address whether the flagella have a direct role in cytokinesis, we treated Giardia with small molecule inhibitors that have been shown to disrupt flagellar function in other systems [Ciliobrevin A, Ciliobrevin D, drug E, drug F, and drug P (53-55)].…”

Section: Giardia Uses a Tubulin Reservoir To Support Rapid Mitosis Anmentioning

confidence: 99%

See 1 more Smart Citation

Myosin-independent cytokinesis in Giardia utilizes flagella to coordinate force generation and direct membrane trafficking

Hardin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

138

View full text Add to dashboard Cite

Devoid of all known canonical actin-binding proteins, the prevalent parasite Giardia lamblia uses an alternative mechanism for cytokinesis. Unique aspects of this mechanism can potentially be leveraged for therapeutic development. Here, live-cell imaging methods were developed for Giardia to establish division kinetics and the core division machinery. Surprisingly, Giardia cytokinesis occurred with a median time that is ∼60 times faster than mammalian cells. In contrast to cells that use a contractile ring, actin was not concentrated in the furrow and was not directly required for furrow progression. Live-cell imaging and morpholino depletion of axonemal Paralyzed Flagella 16 indicated that flagella-based forces initiated daughter cell separation and provided a source for membrane tension. Inhibition of membrane partitioning blocked furrow progression, indicating a requirement for membrane trafficking to support furrow advancement. Rab11 was found to load onto the intracytoplasmic axonemes late in mitosis and to accumulate near the ends of nascent axonemes. These developing axonemes were positioned to coordinate trafficking into the furrow and mark the center of the cell in lieu of a midbody/phragmoplast. We show that flagella motility, Rab11, and actin coordination are necessary for proper abscission. Organisms representing three of the five eukaryotic supergroups lack myosin II of the actomyosin contractile ring. These results support an emerging view that flagella play a central role in cell division among protists that lack myosin II and additionally implicate the broad use of membrane tension as a mechanism to drive abscission.

show abstract

Section: Giardia Uses a Tubulin Reservoir To Support Rapid Mitosis Anmentioning

confidence: 99%

Section: Giardia Uses a Tubulin Reservoir To Support Rapid Mitosis Anmentioning

confidence: 99%

Myosin-independent cytokinesis in Giardia utilizes flagella to coordinate force generation and direct membrane trafficking

Hardin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

138

View full text Add to dashboard Cite

show abstract

“…Given the multiple important roles that flagella play for trypanosomes, these cellular appendages have been studied extensively (3,4). Although studies on axonemal and luminal proteins predominated originally, considerable work has been done more recently on proteins of the trypanosome flagellar membrane (5).…”

mentioning

confidence: 99%

“…These parasites are flagellated in all life cycle stages, including the bloodstream forms (BFs) 4 that infect the mammalian host and in all of the developmental stages that infect the tsetse fly vector. Given the multiple important roles that flagella play for trypanosomes, these cellular appendages have been studied extensively (3,4).…”

mentioning

confidence: 99%

KHARON Is an Essential Cytoskeletal Protein Involved in the Trafficking of Flagellar Membrane Proteins and Cell Division in African Trypanosomes

Sánchez

Tran

Valli

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

African trypanosomes and related kinetoplastid parasites selectively traffic specific membrane proteins to the flagellar membrane, but the mechanisms for this trafficking are poorly understood. We show here that KHARON, a protein originally identified in Leishmania parasites, interacts with a putative trypanosome calcium channel and is required for its targeting to the flagellar membrane. KHARON is located at the base of the flagellar axoneme, where it likely mediates targeting of flagellar membrane proteins, but is also on the subpellicular microtubules and the mitotic spindle. Hence, KHARON is probably a multifunctional protein that associates with several components of the trypanosome cytoskeleton. RNA interference-mediated knockdown of KHARON mRNA results in failure of the calcium channel to enter the flagellar membrane, detachment of the flagellum from the cell body, and disruption of mitotic spindles. Furthermore, knockdown of KHARON mRNA induces a lethal failure of cytokinesis in both bloodstream (mammalian host) and procyclic (insect vector) life cycle stages, and KHARON is thus critical for parasite viability.

show abstract

“…Notably, several flagellar ACs were recently identified that are specifically upregulated in procyclic T. brucei (25), the parasite life cycle stage that undergoes social motility. Given the widespread use of cyclic nucleotides in control of microbial social behavior and the emerging role of the eukaryotic flagellum in coordinating cellular responses to external signals (28,29), we asked whether T. brucei flagellar ACs function in social motility. Here we report that AC6, a procyclic stage-specific AC (25), is localized to the tip of the flagellum and regulates social motility.…”

mentioning

confidence: 99%

Insect Stage-Specific Adenylate Cyclases Regulate Social Motility in African Trypanosomes

2015

Self Cite

View full text Add to dashboard Cite

b Sophisticated systems for cell-cell communication enable unicellular microbes to act as multicellular entities capable of grouplevel behaviors that are not evident in individuals. These group behaviors influence microbe physiology, and the underlying signaling pathways are considered potential drug targets in microbial pathogens. Trypanosoma brucei is a protozoan parasite that causes substantial human suffering and economic hardship in some of the most impoverished regions of the world. T. brucei lives on host tissue surfaces during transmission through its tsetse fly vector, and cultivation on surfaces causes the parasites to assemble into multicellular communities in which individual cells coordinate their movements in response to external signals. This behavior is termed "social motility," based on its similarities with surface-induced social motility in bacteria, and it demonstrates that trypanosomes are capable of group-level behavior. Mechanisms governing T. brucei social motility are unknown. Here we report that a subset of receptor-type adenylate cyclases (ACs) in the trypanosome flagellum regulate social motility. RNA interference-mediated knockdown of adenylate cyclase 6 (AC6), or dual knockdown of AC1 and AC2, causes a hypersocial phenotype but has no discernible effect on individual cells in suspension culture. Mutation of the AC6 catalytic domain phenocopies AC6 knockdown, demonstrating that loss of adenylate cyclase activity is responsible for the phenotype. Notably, knockdown of other ACs did not affect social motility, indicating segregation of AC functions. These studies reveal interesting parallels in systems that control social behavior in trypanosomes and bacteria and provide insight into a feature of parasite biology that may be exploited for novel intervention strategies.

show abstract

Motility and more: the flagellum of Trypanosoma brucei

Cited by 155 publications

References 173 publications

Myosin-independent cytokinesis in Giardia utilizes flagella to coordinate force generation and direct membrane trafficking

Myosin-independent cytokinesis in Giardia utilizes flagella to coordinate force generation and direct membrane trafficking

KHARON Is an Essential Cytoskeletal Protein Involved in the Trafficking of Flagellar Membrane Proteins and Cell Division in African Trypanosomes

Insect Stage-Specific Adenylate Cyclases Regulate Social Motility in African Trypanosomes

Contact Info

Product

Resources

About