Silencing of a putative inner arm dynein heavy chain results in flagellar immotility in Trypanosoma brucei

Springer, Amy L.; Bruhn, David F.; Kinzel, Kathryn W.; Rosenthal, Noël F.; Zukas, Randi; Klingbeil, Michele M.

doi:10.1016/j.molbiopara.2010.09.005

Cited by 16 publications

(13 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, we investigated whether knockdown of TbCentrin3 or TbIAD5‐1 caused any ultra‐structural defects in the axoneme by transmission electron microscopy, and the results showed that there was no detectable structural defect in the axoneme (Fig. F), consistent with the results obtained from the work performed in the procyclic form (Wei et al , ) and from the knockdown of other inner‐arm dynein proteins by others (Springer et al , ; Zukas et al , ). Altogether, these results demonstrated that the TbCentrin3–TbIAD5‐1 complex is required for cytokinesis initiation in bloodstream trypanosomes.…”

Section: Resultssupporting

confidence: 85%

Functional analyses of an axonemal inner‐arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation

Zhang

Lun

et al. 2019

Molecular Microbiology

View full text Add to dashboard Cite

Summary The flagellated eukaryote Trypanosoma brucei alternates between the insect vector and the mammalian host and proliferates through an unusual mode of cell division. Cell division requires flagellum motility‐generated forces, but flagellum motility exerts distinct effects between different life cycle forms. Motility is required for the final cell abscission of the procyclic form in the insect vector, but is necessary for the initiation of cell division of the bloodstream form in the mammalian host. The underlying mechanisms remain elusive. Here we carried out functional analyses of a flagellar axonemal inner‐arm dynein complex in the bloodstream form and investigated its mechanistic role in cytokinesis initiation. We showed that the axonemal inner‐arm dynein heavy chain TbIAD5‐1 and TbCentrin3 form a complex, localize to the flagellum, and are required for viability in the bloodstream form. We further demonstrated the interdependence between TbIAD5‐1 and TbCentrin3 for maintenance of protein stability. Finally, we showed that depletion of TbIAD5‐1 and TbCentrin3 arrested cytokinesis initiation and disrupted the localization of multiple cytokinesis initiation regulators. These findings identified the essential role of an axonemal inner‐arm dynein complex in cell division, and provided molecular insights into the flagellum motility‐mediated cytokinesis initiation in the bloodstream form of T. brucei.

show abstract

Section: Resultssupporting

confidence: 85%

Functional analyses of an axonemal inner‐arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation

Zhang

Lun

et al. 2019

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…1). Similarly, RNAi of another inner-arm dynein, DNAH10, in procyclic trypanosomes also caused severe motility defect, but did not disrupt axoneme structure 15, 16 .…”

Section: Resultsmentioning

confidence: 99%

Centrin3 in trypanosomes maintains the stability of a flagellar inner-arm dynein for cell motility

Wei

Zhao

et al. 2014

Nat Commun

View full text Add to dashboard Cite

Centrin is a conserved component of centrioles in animals and basal bodies in flagellated organisms. It also associates with axonemal inner-arm dyneins and regulates cell motility, but the underlying mechanism remains elusive. In Trypanosoma brucei, three of the five centrins associate with the flagellar basal body, but no centrin has been found to regulate flagellar motility. Here we show that TbCentrin3 is a flagellar protein and knockdown of TbCentrin3 compromises cell motility. Tandem affinity purification followed by mass spectrometry identifies an inner-arm dynein, TbIAD5-1, as the TbCentrin3 partner, and knockdown of TbIAD5-1 causes similar cell motility defect. Further, we demonstrate the interdependence of TbCentrin3 and TbIAD5-1 for maintaining a stable complex in the flagellar axoneme. Together, these results identify the essential role of TbCentrin3 in cell motility by maintaining the stability of an inner-arm dynein in the flagellum, which may be shared by all the centrin-containing flagellated and ciliated organisms.

show abstract

“…These outputs suggest that loss of the cytoplasmic dynein heavy chain (Tb927.7.3160) does not perturb cell cycle distribution; that a putative DNA helicase (Tb927.11.12600) is required for the completion of S phase; and that knockdown of the axonemal dynein heavy chain (Tb927.11.11220) results in endoreduplication in the absence of cytokinesis. Dyneins are cytoskeletal motor proteins that move along microtubules, to produce a flagellar beat, for example (29).…”

Section: A Genome-wide Conditional Knockdown Screen For Cell Cycle Prmentioning

confidence: 99%

Genome-scale functional profiling of cell cycle controls in African trypanosomes

Marques

Tinti

Cassidy

et al. 2020

Preprint

View full text Add to dashboard Cite

Trypanosomatids, which include major pathogens of humans and livestock, are divergent eukaryotes for which cell cycle controls and the underlying mechanisms are not completely understood. Here, we describe a genome-wide RNA-interference library screen for cell cycle regulators in bloodstream form Trypanosoma brucei. We induced massive parallel knockdown and sorted the perturbed population into cell cycle stages using flow cytometry. RNAi-targets were deep-sequenced from each stage and cell cycle profiles were digitally reconstructed at a genomic scale. We identify hundreds of proteins that impact cell cycle progression; glycolytic enzymes required for G1S progression, DNA replication factors, mitosis regulators, proteasome and kinetochore complex components required for G2M progression, flagellar and cytoskeletal components required for cytokinesis, mRNA-binding factors, protein kinases and many previously uncharacterised proteins. The outputs facilitate functional annotation and drug-target prioritisation and provide comprehensive functional genomic evidence for the machineries, pathways and regulators that coordinate progression through the trypanosome cell cycle.The data can be searched and browsed using an interactive, open access, online data visualization tool (https://tryp-cycle.onrender.com).

show abstract

Silencing of a putative inner arm dynein heavy chain results in flagellar immotility in Trypanosoma brucei

Cited by 16 publications

References 48 publications

Functional analyses of an axonemal inner‐arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation

Functional analyses of an axonemal inner‐arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation

Centrin3 in trypanosomes maintains the stability of a flagellar inner-arm dynein for cell motility

Genome-scale functional profiling of cell cycle controls in African trypanosomes

Contact Info

Product

Resources

About