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Molecular Researches on Cilia
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Molecular Researches on Cilia

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 20854

Special Issue Editors

Prof. Dr. Takashi Nakahari

E-Mail Website
Guest Editor
Research Unit for Epithelial Physiology, Research Organization of Science and Technology, BKC Ritsumeikan University, Kusatsu 525-8755, Shiga, Japan
Interests: motile cilia; airway biology; epithelial ion transport; cell signaling; intracellular Cl-signaling; cell volume regulation
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Shinji Asano

E-Mail Website
Guest Editor
Faculty of Pharmaceutical Science, Ritsumeikan University, Kusatsu, Japan
Interests: transporter; Ezrin/Radixin/Moesin (ERM) protein; cytoskeleton; gastric acid secretion; proton pump; motile cilium and so on
Dr. kawaguchi kotoku

E-Mail
Guest Editor
Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Japan
Interests: cytoskeletal organization; motile cilia; epithelial transport; transporters disease

Special Issue Information

Dear Colleagues,

Cilia, which are highly conserved, hair-like organelles projecting from the apical cell surface, have various functions in human health and development. The core structure of cilia consists of nine microtubule doublets, A and B tubules, surrounding a central pair of microtubules (9+2 structure) or lacking a central pair of microtubules (9+0 structure). Motile 9+2 cilia function mainly as motor organelles, whereas non-motile 9+0 cilia function as the receptor of sensory systems. Inherited or aquired disorders of cilia are known as motile ciliopathies or immotile ciliopathies. Clinical ciliopathy studies have revealed overlapping features between both ciliopathies in relation to situs inversus totalis, infertility, and hydrocephalus. However, at present, we have only limited knowledge with which to counter genetic and acquired disorders of cilia.  

Recent advances in the molecular research of cilia have revealed various functions of cilia, and helped increase our knowledge of cilia functions in health and disease through genetic, molecular, and cell biological insights. In this Special Issue, we would like to summarize evidence and challenges in recent molecular research on cilia.

Prof. Takashi Nakahari
Prof. Shinji Asano
Guest Editors

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Keywords

  • cilium
  • flagella
  • airways
  • brain ventricle
  • ependymal cilia
  • hydrocephalus
  • fallopian tube
  • sperm
  • infertility
  • ciliopathy
  • dyneins
  • axoneme
  • L-R asymmetry
  • ciliogenesis
  • planer cell polarity
  • intraflagellar transport

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Published Papers (4 papers)

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Research

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16 pages, 2002 KiB  
Article
Airway Ciliary Beating Affected by the Pcp4 Dose-Dependent [Ca2+]i Increase in Down Syndrome Mice, Ts1Rhr
by Haruka Kogiso, Matthieu Raveau, Kazuhiro Yamakawa, Daichi Saito, Yukiko Ikeuchi, Tomonori Okazaki, Shinji Asano, Toshio Inui, Yoshinori Marunaka and Takashi Nakahari
Int. J. Mol. Sci. 2020, 21(6), 1947; https://doi.org/10.3390/ijms21061947 - 12 Mar 2020
Cited by 5 | Viewed by 3109
Abstract
In Ts1Rhr, a Down syndrome model mouse, the airway ciliary beatings are impaired; that is, decreases in ciliary beat frequency (CBF) and ciliary bend angle (CBA, an index of ciliary beat amplitude)). A resumption to two copies of the Pcp4 gene on the [...] Read more.
In Ts1Rhr, a Down syndrome model mouse, the airway ciliary beatings are impaired; that is, decreases in ciliary beat frequency (CBF) and ciliary bend angle (CBA, an index of ciliary beat amplitude)). A resumption to two copies of the Pcp4 gene on the Ts1Rhr trisomic segment (Ts1Rhr:Pcp4+/+/-) rescues the decreases in CBF and CBA that occur in Ts1Rhr. In airway cilia, upon stimulation with procaterol (a β2-agonist), the CBF increase is slower over the time course than the CBA increase because of cAMP degradation by Ca2+/calmodulin-dependent phosphodiesterase 1 (PDE1) existing in the metabolon regulating CBF. In Ts1Rhr, procaterol-stimulated CBF increase was much slower over the time course than in the wild-type mouse (Wt) or Ts1Rhr:Pcp4+/+/-. However, in the presence of 8MmIBMX (8-methoxymethyl isobutylmethyl xanthine, an inhibitor of PDE1) or calmidazolium (an inhibitor of calmodulin), in both Wt and Ts1Rhr, procaterol stimulates CBF and CBA increases over a similar time course. Measurements of cAMP revealed that the cAMP contents were lower in Ts1Rhr than in Wt or in Ts1Rhr:Pcp4+/+/-, suggesting the activation of PDE1A that is present in Ts1Rhr airway cilia. Measurements of the intracellular Ca2+ concentration ([Ca2+]i) in airway ciliary cells revealed that temperature (increasing from 25 to 37 °C) or 4αPDD (a selective transient receptor potential vanilloid 4 (TRPV4) agonist) stimulates a larger [Ca2+]i increase in Ts1Rhr than in Wt or Ts1Rhr:Pcp4+/+/-. In airway ciliary cells of Ts1Rhr, Pcp4-dose dependent activation of TRPV4 appears to induce an increase in the basal [Ca2+]i. In early embryonic day mice, a basal [Ca2+]i increased by PCP4 expressed may affect axonemal regulatory complexes regulated by the Ca2+-signal in Ts1Rhr, leading to a decrease in the basal CBF and CBA of airway cilia. Full article
(This article belongs to the Special Issue Molecular Researches on Cilia)
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Review

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21 pages, 8586 KiB  
Review
Central Apparatus, the Molecular Kickstarter of Ciliary and Flagellar Nanomachines
by Zuzanna Samsel, Justyna Sekretarska, Anna Osinka, Dorota Wloga and Ewa Joachimiak
Int. J. Mol. Sci. 2021, 22(6), 3013; https://doi.org/10.3390/ijms22063013 - 16 Mar 2021
Cited by 13 | Viewed by 4997
Abstract
Motile cilia and homologous organelles, the flagella, are an early evolutionarily invention, enabling primitive eukaryotic cells to survive and reproduce. In animals, cilia have undergone functional and structural speciation giving raise to typical motile cilia, motile nodal cilia, and sensory immotile cilia. In [...] Read more.
Motile cilia and homologous organelles, the flagella, are an early evolutionarily invention, enabling primitive eukaryotic cells to survive and reproduce. In animals, cilia have undergone functional and structural speciation giving raise to typical motile cilia, motile nodal cilia, and sensory immotile cilia. In contrast to other cilia types, typical motile cilia are able to beat in complex, two-phase movements. Moreover, they contain many additional structures, including central apparatus, composed of two single microtubules connected by a bridge-like structure and assembling numerous complexes called projections. A growing body of evidence supports the important role of the central apparatus in the generation and regulation of the motile cilia movement. Here we review data concerning the central apparatus structure, protein composition, and the significance of its components in ciliary beating regulation. Full article
(This article belongs to the Special Issue Molecular Researches on Cilia)
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18 pages, 14018 KiB  
Review
Intracellular Cl− Regulation of Ciliary Beating in Ciliated Human Nasal Epithelial Cells: Frequency and Distance of Ciliary Beating Observed by High-Speed Video Microscopy
by Makoto Yasuda, Taka-aki Inui, Shigeru Hirano, Shinji Asano, Tomonori Okazaki, Toshio Inui, Yoshinori Marunaka and Takashi Nakahari
Int. J. Mol. Sci. 2020, 21(11), 4052; https://doi.org/10.3390/ijms21114052 - 5 Jun 2020
Cited by 14 | Viewed by 4249
Abstract
Small inhaled particles, which are entrapped by the mucous layer that is maintained by mucous secretion via mucin exocytosis and fluid secretion, are removed from the nasal cavity by beating cilia. The functional activities of beating cilia are assessed by their frequency and [...] Read more.
Small inhaled particles, which are entrapped by the mucous layer that is maintained by mucous secretion via mucin exocytosis and fluid secretion, are removed from the nasal cavity by beating cilia. The functional activities of beating cilia are assessed by their frequency and the amplitude. Nasal ciliary beating is controlled by intracellular ions (Ca2+, H+ and Cl−), and is enhanced by a decreased concentration of intracellular Cl− ([Cl−]i) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which increases the ciliary beat amplitude. A novel method to measure both ciliary beat frequency (CBF) and ciliary beat distance (CBD, an index of ciliary beat amplitude) in cHNECs has been developed using high-speed video microscopy, which revealed that a decrease in [Cl−]i increased CBD, but not CBF, and an increase in [Cl−]i decreased both CBD and CBF. Thus, [Cl−]i inhibits ciliary beating in cHNECs, suggesting that axonemal structures controlling CBD and CBF may have Cl− sensors and be regulated by [Cl−]i. These observations indicate that the activation of Cl− secretion stimulates ciliary beating (increased CBD) mediated via a decrease in [Cl−]i in cHNECs. Thus, [Cl−]i is critical for controlling ciliary beating in cHNECs. This review introduces the concept of Cl− regulation of ciliary beating in cHNECs. Full article
(This article belongs to the Special Issue Molecular Researches on Cilia)
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17 pages, 2462 KiB  
Review
Force-Generating Mechanism of Axonemal Dynein in Solo and Ensemble
by Kenta Ishibashi, Hitoshi Sakakibara and Kazuhiro Oiwa
Int. J. Mol. Sci. 2020, 21(8), 2843; https://doi.org/10.3390/ijms21082843 - 18 Apr 2020
Cited by 10 | Viewed by 7558
Abstract
In eukaryotic cilia and flagella, various types of axonemal dyneins orchestrate their distinct functions to generate oscillatory bending of axonemes. The force-generating mechanism of dyneins has recently been well elucidated, mainly in cytoplasmic dyneins, thanks to progress in single-molecule measurements, X-ray crystallography, and [...] Read more.
In eukaryotic cilia and flagella, various types of axonemal dyneins orchestrate their distinct functions to generate oscillatory bending of axonemes. The force-generating mechanism of dyneins has recently been well elucidated, mainly in cytoplasmic dyneins, thanks to progress in single-molecule measurements, X-ray crystallography, and advanced electron microscopy. These techniques have shed light on several important questions concerning what conformational changes accompany ATP hydrolysis and whether multiple motor domains are coordinated in the movements of dynein. However, due to the lack of a proper expression system for axonemal dyneins, no atomic coordinates of the entire motor domain of axonemal dynein have been reported. Therefore, a substantial amount of knowledge on the molecular architecture of axonemal dynein has been derived from electron microscopic observations on dynein arms in axonemes or on isolated axonemal dynein molecules. This review describes our current knowledge and perspectives of the force-generating mechanism of axonemal dyneins in solo and in ensemble. Full article
(This article belongs to the Special Issue Molecular Researches on Cilia)
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