Mechanosignaling between central apparatus and radial spokes controls axonemal dynein activity

Oda, Toshiyuki; Yanagisawa, Haruaki; Yagi, Toshiki; Kikkawa, Masahide

doi:10.1085/jgp.1434oia11

Cited by 12 publications

(23 citation statements)

References 36 publications

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“…The low incidence of and sometimes intermittent CP loss observed in airway cilia of PCD patients with RS gene mutations suggests that the RS head‐CP apparatus interaction also has a role to stabilise the CP against possible ciliary beat‐induced lesions, in addition to the canonical role of mechanosignaling [Castleman et al., ; Zietkiewicz et al., ; Daniels et al., ; Kott et al., ; Knowles et al., ; Lin et al., ; Oda et al., ; Onoufriadis et al., ; Frommer et al., ]. Our results suggest that the protection effect is even more important in ependymal cilia based on the Rsph9 depletion‐induced near complete disruption of the CP (Figure ).…”

Section: Discussionmentioning

confidence: 99%

“…The vast majority of motile cilia are composed of nine outer MT doublets that surround a central pair (CP) of MTs (‘9+2’ arrangement), whereas most immotile, or primary, cilia lack the CP (‘9+0’ arrangement). The CP is surrounded by associated proteinous projections to form the CP apparatus, which contacts with radial spokes (RSs), T‐shaped macromolecular structures protruding from the outer MT doublets (Figure A), to regulate the ciliary motility [Pigino et al., ; Oda et al., ; Satir et al., ; Ishikawa, ]. In mammals, the ‘9+2’‐type cilia are present in sperms and epithelia of the airway, ependyma, oviduct and epididymis.…”

Section: Introductionmentioning

confidence: 99%

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Rsph9 is critical for ciliary radial spoke assembly and central pair microtubule stability

Zhu

Líu

Chen

et al. 2018

Biology of the Cell

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Background Information In the “9+2”‐type motile cilia, radial spokes (RSs) protruded from the nine peripheral microtubule doublets surround and interact with the central pair (CP) apparatus to regulate ciliary beat. RSPH9 is the human homologue of the essential protozoan RS head protein Rsp9. Its mutations in human primary ciliary dyskinesia patients, however, cause CP loss in a small portion of airway cilia without affecting the ciliary localization of other head proteins. Results We characterized mouse Rsph9 and investigated its function in ependymal motile cilia. Rsph9 was specifically expressed in mouse tissues containing motile cilia and upregulated during multiciliation. Its ciliary localization complied with its putative role as an RS subunit. Depletion of Rsph9 by RNAi in mouse ependymal cilia resulted in a near complete CP loss and altered the ciliary beat pattern from planar to rotational. Multiple RS proteins, including those in the head, were also markedly downregulated in the Rsph9‐depleted cilia. Conclusion Rsph9 is essential for both the RS head assembly and the CP maintenance in mammalian ependymal cilia. Significance Our results help to understand the assembly and functions of mammalian RS and pathology of RS‐related ciliopathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rsph9 is critical for ciliary radial spoke assembly and central pair microtubule stability

Zhu

Líu

Chen

et al. 2018

Biology of the Cell

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“…Recent evidence from Kikkawa's laboratory [Oda et al, ] suggests that the spoke head is important as a mechanical spacer. They showed that substituting an unrelated protein of suitable size to the radial spoke heads in a central pair projection deficient strain of Chlamydomonas was sufficient to restore motility.…”

Section: Discussionmentioning

confidence: 99%

Mechanics of the eukaryotic flagellar axoneme: Evidence for structural distortion during bending

et al. 2016

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The sliding doublet mechanism is the established explanation that allows us to understand the process of ciliary and flagellar bending. In this study, we apply the principles of the sliding doublet mechanism to analyze the mechanics of the counterbend phenomenon in sea urchin sperm flagella. When a passive, vanadate-treated, flagellum is forced into a bend with a glass microprobe, the portion of the flagellum distal to the probe exhibits a bend of opposite curvature (counterbend) to the imposed bend. This phenomenon was shown to be caused by the induction of inter-doublet shear and is dependent on the presence of an inter-doublet shear resistance. Here we report that in sea urchin flagella there is systematically less shear induced in the distal flagellum than is predicted by the sliding doublet mechanism, if we follow the assumption that the diameter of the flagellum is uniform. To account for the reduced shear that is observed, the likeliest and most direct interpretation is that the portion of the axoneme that is forced to bend undergoes substantial compression of the axoneme in the bending plane. A compression of 30-50 nm would be sufficient to account for the shear reduction from a bend of 2 radians. A compression of this magnitude would require considerable flexibility in the axoneme structure. This would necessitate that the radial spokes and/or the central pair apparatus are easily compressed by transverse stress. © 2016 Wiley Periodicals, Inc.

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“…7 These RS interactions are believed to transmit a mechanochemical signal to outer microtubule doublets and locally control dynein-driven microtubule sliding. 8,9 In the flagellated alga Chlamydomonas reinhardtii, the RSs are composed of at least 23 proteins. 6 However, a recent study performed on respiratory cilia by means of cryo-electron tomography has revealed that RSs are structurally different in humans.…”

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confidence: 99%

RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes

Jeanson

Copin

Papon

et al. 2015

The American Journal of Human Genetics

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Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive condition resulting from structural and/or functional defects of the axoneme in motile cilia and sperm flagella. The great majority of mutations identified so far involve genes whose defects result in dynein-arm anomalies. By contrast, PCD due to CC/RS defects (those in the central complex [CC] and radial spokes [RSs]), which might be difficult to diagnose, remains mostly unexplained. We identified non-ambiguous RSPH3 mutations in 5 of 48 independent families affected by CC/RS defects. RSPH3, whose ortholog in the flagellated alga Chlamydomonas reinhardtii encodes a RS-stalk protein, is mainly expressed in respiratory and testicular cells. Its protein product, which localizes within the cilia of respiratory epithelial cells, was undetectable in airway cells from an individual with RSPH3 mutations and in whom RSPH23 (a RS-neck protein) and RSPH1 and RSPH4A (RS-head proteins) were found to be still present within cilia. In the case of RSPH3 mutations, high-speed-videomicroscopy analyses revealed the coexistence of immotile cilia and motile cilia with movements of reduced amplitude. A striking feature of the ultrastructural phenotype associated with RSPH3 mutations is the near absence of detectable RSs in all cilia in combination with a variable proportion of cilia with CC defects. Overall, this study shows that RSPH3 mutations contribute to disease in more than 10% of PCD-affected individuals with CC/RS defects, thereby allowing an accurate diagnosis to be made in such cases. It also unveils the key role of RSPH3 in the proper building of RSs and the CC in humans.

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Mechanosignaling between central apparatus and radial spokes controls axonemal dynein activity

Cited by 12 publications

References 36 publications

Rsph9 is critical for ciliary radial spoke assembly and central pair microtubule stability

Rsph9 is critical for ciliary radial spoke assembly and central pair microtubule stability

Mechanics of the eukaryotic flagellar axoneme: Evidence for structural distortion during bending

RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes

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