Structural analysis of flagellar axonemes from inner arm dynein knockdown strains of Trypanosoma brucei

Zukas, Randi; Chang, Alex J.; Rice, Marian; Springer, Amy L.

doi:10.32604/biocell.2012.36.133

Cited by 12 publications

(5 citation statements)

References 32 publications

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“…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: 98%

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

Wei

Zhao

et al. 2014

Nat Commun

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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.

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“…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: 98%

“…For classification of runner, tumbler and immotile cells, we followed the criteria reported in previous publications 16 , 41 . Briefly, runner cells were classified as being able to move a long distance from one place to another.…”

Section: Methodsmentioning

confidence: 99%

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

Wei

Zhao

et al. 2014

Nat Commun

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“…Dnah10 function is required for ependymal cilia motility in the ventricular system Dnah10 (called DHC1 in Chlamydomonas) functions as an inner arm dynein motor of motile cilia, leading to reduced motility when mutated in Chlamydomonas (Myster, Knott et al 1997, Kamiya andYagi 2014). DNAH10 knockdown in the Trypanosoma brucei agellate caused severe motility defects of cilia, without obvious ultrastructural defects of the axoneme (Zukas, Chang et al 2012). To determine whether dnah10 ut28/ut28 mutant zebra sh show alterations in the development or motility of motile cilia in the central canal we crossed it to a transgenic Tg(Foxj1a:Arl13B-GFP) ut22 strain, which labels motile ependymal cilia in the brain and central canal of zebra sh (Konjikusic, Yeetong et al 2018), without affecting the body axis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Rare coding variants in axonemal dynein heavy chain genes are associated with adolescent idiopathic scoliosis

Wang

Liu

Yang

et al. 2020

Preprint

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Adolescent idiopathic scoliosis (AIS) is the most common pediatric musculoskeletal disorder worldwide, characterized by atypical spine curvatures in otherwise healthy children. Human genetic studies have identified candidate genes associated with AIS, however, only a few of these genes have been shown to recapitulate adult-viable scoliosis in animal models. To further define susceptibility loci for AIS, we performed whole exome sequencing on a cohort of 195 Han Chinese AIS patients and 229 healthy controls. We identified members of the axonemal dynein family associated with both sporadic and familial AIS. We demonstrate that disruption of the dynein axonemal heavy chain 10 (dnah10) gene results in recessive adult-viable scoliosis in zebrafish. These dnah10 mutant zebrafish display reduced ependymal cilia beating and a disassembly of the Reissner fiber in the hindbrain and spinal canal, concurrent with the onset of body curvatures. Altogther, these results demonstrate that mutations in axonemal dynein genes are linked with human AIS and suggest that ependymal cell cilia function plays an essential role in maintaining spine alignment in humans.

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“…The DNAH gene family codes for chain proteins of the microtubuleassociated motor protein dynein, which is found in cilia and flagella. Their gene products play an essential role for correct cilia function, including cilia motility [70][71][72][73][74][75]. Both, the IFT complex and the motor protein dynein play an important role in the signal transduction of embryological signaling pathways [16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Genetic Disruption of Cilia-Associated Signaling Pathways in Patients with VACTERL Association

Ritter,

Lisec,

Klinner

et al. 2023

Children

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VACTERL association is a rare malformation complex consisting of vertebral defects, anorectal malformation, cardiovascular defects, tracheoesophageal fistulae with esophageal atresia, renal malformation, and limb anomalies. According to current knowledge, VACTERL is based on a multifactorial pathogenesis including genomic alterations. This study aimed to improve the understanding of the genetic mechanisms in the development of VACTERL by investigating the genetic background with a focus on signaling pathways and cilia function. The study was designed as genetic association study. For this, whole-exome sequencing with subsequent functional enrichment analyses was performed for 21 patients with VACTERL or a VACTERL-like phenotype. In addition, whole-exome sequencing was performed for three pairs of parents and Sanger-sequencing was performed for ten pairs of parents. Analysis of the WES-data revealed genetic alteration in the Shh- and Wnt-signaling pathways. Additional performed functional enrichment analysis identified an overrepresentation of the cilia, including 47 affected ciliary genes with clustering in the DNAH gene family and the IFT-complex. The examination of the parents showed that most of the genetic changes were inherited. In summary, this study indicates three genetically determined damage mechanisms for VACTERL with the potential to influence each other, namely Shh- and Wnt-signaling pathway disruption, structural cilia defects and disruption of the ciliary signal transduction.

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Structural analysis of flagellar axonemes from inner arm dynein knockdown strains of Trypanosoma brucei

Cited by 12 publications

References 32 publications

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

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

Rare coding variants in axonemal dynein heavy chain genes are associated with adolescent idiopathic scoliosis

Genetic Disruption of Cilia-Associated Signaling Pathways in Patients with VACTERL Association

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