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Cilia and Flagella: Structure, Function and Beyond
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Cilia and Flagella: Structure, Function and Beyond

A topical collection in Cells (ISSN 2073-4409). This collection belongs to the section "Intracellular and Plasma Membranes".

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Editors

Dr. William Tsang

E-Mail Website
Collection Editor
Institut de Recherches Cliniques de Montréal (IRCM) Research Unit Director, Cell Division and Centrosome Biology, 110 Avenue des Pins Ouest, Montréal, QC, Canada
Interests: centrosome; cilia; cancer; ciliopathy; cell cycle; cell division; microtubule; cell biology; molecular biology; biochemistry; genetics
Special Issues, Collections and Topics in MDPI journals
Dr. Gang Dong

E-Mail Website
Collection Editor
Computational and Structural Biology, Max F. Perutz Laboratories, Medical University of Vienna, Vienna, Austria
Interests: structural biology; vesicular traffic; cilium biogenesis
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Cilia and flagella are antenna-like protrusions present on many types of eukaryotic cells. Consequently, they have evolved to perform diverse functions, such as locomotion, mucus clearance, fluid circulation, chemosensation, and mechanosensation. It is now known that defects in cilia and flagella assembly or function give rise to a wide spectrum of human diseases including infertility, loss of vision, kidney cysts, respiratory defects, skeletal anomalies, and neurological disorders. In spite of functional differences, cilia and flagella are remarkably similar in terms of molecular composition and structure, consisting of stabilized microtubules arranged in a nine-fold radial symmetry. Cilia and flagella were originally discovered centuries ago, yet many aspects regarding their structure and function are just beginning to emerge, thanks in part to breakthrough technologies, such as super-resolution microscopy, cryo-electron microscopy, and BioID. This Topical Collection focuses on current advances in the biology of cilia and flagella. We welcome contributions that include, but are not limited to, structural and functional studies of cilia/flagella, different cilia/flagella model systems, mechanisms of cilia/flagella assembly, maintenance, and disassembly, mechanisms of cilia/flagella-mediated sensing mechanisms and signal transduction, link between cilia/flagella and the cell cycle or other relevant cell physiological processes implicated in disease. Submitted articles will be peer reviewed in accordance with the journal’s policy. The Collection Editors declare no competing interests.

Dr. William Tsang
Dr. Gang Dong
Collection Editors

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Keywords

  • cilia
  • flagella
  • centrioles
  • basal bodies
  • centrosomes
  • axonemes
  • microtubules
  • ciliogenesis
  • ciliopathies

Published Papers (17 papers)

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2021

Jump to: 2020, 2019, 2018

21 pages, 9684 KiB  
Article
Trace Amine-Associated Receptor 1 Trafficking to Cilia of Thyroid Epithelial Cells
by Maria Qatato, Vaishnavi Venugopalan, Alaa Al-Hashimi, Maren Rehders, Aaron D. Valentine, Zeynep Hein, Uillred Dallto, Sebastian Springer and Klaudia Brix
Cells 2021, 10(6), 1518; https://doi.org/10.3390/cells10061518 - 16 Jun 2021
Cited by 5 | Viewed by 2777
Abstract
Trace amine-associated receptor 1 (rodent Taar1/human TAAR1) is a G protein-coupled receptor that is mainly recognized for its functions in neuromodulation. Previous in vitro studies suggested that Taar1 may signal from intracellular compartments. However, we have shown Taar1 to localize apically and on [...] Read more.
Trace amine-associated receptor 1 (rodent Taar1/human TAAR1) is a G protein-coupled receptor that is mainly recognized for its functions in neuromodulation. Previous in vitro studies suggested that Taar1 may signal from intracellular compartments. However, we have shown Taar1 to localize apically and on ciliary extensions in rodent thyrocytes, suggesting that at least in the thyroid, Taar1 may signal from the cilia at the apical plasma membrane domain of thyrocytes in situ, where it is exposed to the content of the follicle lumen containing putative Taar1 ligands. This study was designed to explore mouse Taar1 (mTaar1) trafficking, heterologously expressed in human and rat thyroid cell lines in order to establish an in vitro system in which Taar1 signaling from the cell surface can be studied in future. The results showed that chimeric mTaar1-EGFP traffics to the apical cell surface and localizes particularly to spherical structures of polarized thyroid cells, procilia, and primary cilia upon serum-starvation. Moreover, mTaar1-EGFP appears to form high molecular mass forms, possibly homodimers and tetramers, in stably expressing human thyroid cell lines. However, only monomeric mTaar1-EGFP was cell surface biotinylated in polarized human thyrocytes. In polarized rat thyrocytes, mTaar1-EGFP is retained in the endoplasmic reticulum, while cilia were reached by mTaar1-EGFP transiently co-expressed in combination with an HA-tagged construct of the related mTaar5. We conclude that Taar1 trafficking to cilia depends on their integrity. The results further suggest that an in vitro cell model was established that recapitulates Taar1 trafficking in thyrocytes in situ, in principle, and will enable studying Taar1 signaling in future, thus extending our general understanding of its potential significance for thyroid autoregulation. Full article
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19 pages, 2780 KiB  
Review
Primary Cilium Is Involved in Stem Cell Differentiation and Renewal through the Regulation of Multiple Signaling Pathways
by Sila Yanardag and Elena N. Pugacheva
Cells 2021, 10(6), 1428; https://doi.org/10.3390/cells10061428 - 08 Jun 2021
Cited by 17 | Viewed by 7446
Abstract
Signaling networks guide stem cells during their lineage specification and terminal differentiation. Primary cilium, an antenna-like protrusion, directly or indirectly plays a significant role in this guidance. All stem cells characterized so far have primary cilia. They serve as entry- or check-points for [...] Read more.
Signaling networks guide stem cells during their lineage specification and terminal differentiation. Primary cilium, an antenna-like protrusion, directly or indirectly plays a significant role in this guidance. All stem cells characterized so far have primary cilia. They serve as entry- or check-points for various signaling events by controlling the signal transduction and stability. Thus, defects in the primary cilia formation or dynamics cause developmental and health problems, including but not limited to obesity, cardiovascular and renal anomalies, hearing and vision loss, and even cancers. In this review, we focus on the recent findings of how primary cilium controls various signaling pathways during stem cell differentiation and identify potential gaps in the field for future research. Full article
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2020

Jump to: 2021, 2019, 2018

22 pages, 919 KiB  
Review
Regulation of the Extracellular Matrix by Ciliary Machinery
by Collins I and Wann A.K.T
Cells 2020, 9(2), 278; https://doi.org/10.3390/cells9020278 - 23 Jan 2020
Cited by 17 | Viewed by 4957
Abstract
The primary cilium is an organelle involved in cellular signalling. Mutations affecting proteins involved in cilia assembly or function result in diseases known as ciliopathies, which cause a wide variety of phenotypes across multiple tissues. These mutations disrupt various cellular processes, including regulation [...] Read more.
The primary cilium is an organelle involved in cellular signalling. Mutations affecting proteins involved in cilia assembly or function result in diseases known as ciliopathies, which cause a wide variety of phenotypes across multiple tissues. These mutations disrupt various cellular processes, including regulation of the extracellular matrix. The matrix is important for maintaining tissue homeostasis through influencing cell behaviour and providing structural support; therefore, the matrix changes observed in ciliopathies have been implicated in the pathogenesis of these diseases. Whilst many studies have associated the cilium with processes that regulate the matrix, exactly how these matrix changes arise is not well characterised. This review aims to bring together the direct and indirect evidence for ciliary regulation of matrix, in order to summarise the possible mechanisms by which the ciliary machinery could regulate the composition, secretion, remodelling and organisation of the matrix. Full article
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2019

Jump to: 2021, 2020, 2018

14 pages, 7868 KiB  
Article
Estrogen and EGFR Pathways Regulate Notch Signaling in Opposing Directions for Multi-Ciliogenesis in the Fallopian Tube
by Maobi Zhu, Tomohiko Iwano and Sen Takeda
Cells 2019, 8(8), 933; https://doi.org/10.3390/cells8080933 - 19 Aug 2019
Cited by 19 | Viewed by 4456
Abstract
The lumen of the fallopian tube (FT) is lined with columnar epithelium composed of secretory and ciliated cells, both of which are important for reproduction. However, the molecular mechanism regulating cell fate remains controversial. In this study, we established a primary culture system [...] Read more.
The lumen of the fallopian tube (FT) is lined with columnar epithelium composed of secretory and ciliated cells, both of which are important for reproduction. However, the molecular mechanism regulating cell fate remains controversial. In this study, we established a primary culture system using porcine fallopian tube epithelial cells (FTECs) to study the differentiation mechanism. We found that estrogen promoted the differentiation of multi-ciliated cells (MCCs) through estrogen receptor β, following the reduction of DLL1, a ligand of Notch. Meanwhile, epidermal growth factor (EGF), a regulator of epithelial homeostasis and differentiation, suppressed ciliogenesis by the activation of Notch signaling. However, the estrogen pathway did not affect the activation of the EGF pathway. Taken together, the differentiation of MMCs in FT depends on the balance of EGF and estrogen signaling, either of which inhibits or stimulates the Notch signaling pathway respectively. Full article
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18 pages, 814 KiB  
Review
The Autophagy-Cilia Axis: An Intricate Relationship
by Manuela Morleo and Brunella Franco
Cells 2019, 8(8), 905; https://doi.org/10.3390/cells8080905 - 15 Aug 2019
Cited by 26 | Viewed by 6975
Abstract
Primary cilia are microtubule-based organelles protruding from the surface of almost all vertebrate cells. This organelle represents the cell’s antenna which acts as a communication hub to transfer extracellular signals into intracellular responses during development and in tissue homeostasis. Recently, it has been [...] Read more.
Primary cilia are microtubule-based organelles protruding from the surface of almost all vertebrate cells. This organelle represents the cell’s antenna which acts as a communication hub to transfer extracellular signals into intracellular responses during development and in tissue homeostasis. Recently, it has been shown that loss of cilia negatively regulates autophagy, the main catabolic route of the cell, probably utilizing the autophagic machinery localized at the peri-ciliary compartment. On the other side, autophagy influences ciliogenesis in a context-dependent manner, possibly to ensure that the sensing organelle is properly formed in a feedback loop model. In this review we discuss the recent literature and propose that the autophagic machinery and the ciliary proteins are functionally strictly related to control both autophagy and ciliogenesis. Moreover, we report examples of diseases associated with autophagic defects which cause cilia abnormalities, and propose and discuss the hypothesis that, at least some of the clinical manifestations observed in human diseases associated to ciliary disfunction may be the result of a perturbed autophagy. Full article
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25 pages, 2353 KiB  
Review
A Ciliary View of the Immunological Synapse
by Chiara Cassioli and Cosima T. Baldari
Cells 2019, 8(8), 789; https://doi.org/10.3390/cells8080789 - 29 Jul 2019
Cited by 34 | Viewed by 7698
Abstract
The primary cilium has gone from being a vestigial organelle to a crucial signaling hub of growing interest given the association between a group of human disorders, collectively known as ciliopathies, and defects in its structure or function. In recent years many ciliogenesis [...] Read more.
The primary cilium has gone from being a vestigial organelle to a crucial signaling hub of growing interest given the association between a group of human disorders, collectively known as ciliopathies, and defects in its structure or function. In recent years many ciliogenesis proteins have been observed at extraciliary sites in cells and likely perform cilium-independent functions ranging from regulation of the cytoskeleton to vesicular trafficking. Perhaps the most striking example is the non-ciliated T lymphocyte, in which components of the ciliary machinery are repurposed for the assembly and function of the immunological synapse even in the absence of a primary cilium. Furthermore, the specialization traits described at the immunological synapse are similar to those seen in the primary cilium. Here, we review common regulators and features shared by the immunological synapse and the primary cilium that document the remarkable homology between these structures. Full article
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15 pages, 2417 KiB  
Review
Mathematical Modeling of Mucociliary Clearance: A Mini-Review
by Ling Xu and Yi Jiang
Cells 2019, 8(7), 736; https://doi.org/10.3390/cells8070736 - 18 Jul 2019
Cited by 18 | Viewed by 5115
Abstract
Mucociliary clearance is an important innate host defense of the mammalian respiratory system, as it traps foreign substances, including pollutants, pathogens, and allergens, and transports them out of the airway. The underlying mechanism of the actuation and coordination of cilia, the interplay between [...] Read more.
Mucociliary clearance is an important innate host defense of the mammalian respiratory system, as it traps foreign substances, including pollutants, pathogens, and allergens, and transports them out of the airway. The underlying mechanism of the actuation and coordination of cilia, the interplay between the cilia and mucus, and the formation of the metachronal wave have been explored extensively both experimentally and mathematically. In this mini-review, we provide a survey of the mathematical models of mucociliary clearance, from the motion of one single cilium to the emergence of the metachronal wave in a group of them, from the fundamental theoretical study to the state-of-the-art three-dimensional simulations. The mechanism of cilium actuation is discussed, together with the mathematical simplification and the implications or caveats of the results. Full article
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22 pages, 1668 KiB  
Review
Ciliary Proteins: Filling the Gaps. Recent Advances in Deciphering the Protein Composition of Motile Ciliary Complexes
by Anna Osinka, Martyna Poprzeczko, Magdalena M. Zielinska, Hanna Fabczak, Ewa Joachimiak and Dorota Wloga
Cells 2019, 8(7), 730; https://doi.org/10.3390/cells8070730 - 17 Jul 2019
Cited by 27 | Viewed by 7023
Abstract
Cilia are highly evolutionarily conserved, microtubule-based cell protrusions present in eukaryotic organisms from protists to humans, with the exception of fungi and higher plants. Cilia can be broadly divided into non-motile sensory cilia, called primary cilia, and motile cilia, which are locomotory organelles. [...] Read more.
Cilia are highly evolutionarily conserved, microtubule-based cell protrusions present in eukaryotic organisms from protists to humans, with the exception of fungi and higher plants. Cilia can be broadly divided into non-motile sensory cilia, called primary cilia, and motile cilia, which are locomotory organelles. The skeleton (axoneme) of primary cilia is formed by nine outer doublet microtubules distributed on the cilium circumference. In contrast, the skeleton of motile cilia is more complex: in addition to outer doublets, it is composed of two central microtubules and several diverse multi-protein complexes that are distributed periodically along both types of microtubules. For many years, researchers have endeavored to fully characterize the protein composition of ciliary macro-complexes and the molecular basis of signal transduction between these complexes. Genetic and biochemical analyses have suggested that several hundreds of proteins could be involved in the assembly and function of motile cilia. Within the last several years, the combined efforts of researchers using cryo-electron tomography, genetic and biochemical approaches, and diverse model organisms have significantly advanced our knowledge of the ciliary structure and protein composition. Here, we summarize the recent progress in the identification of the subunits of ciliary complexes, their precise intraciliary localization determined by cryo-electron tomography data, and the role of newly identified proteins in cilia. Full article
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20 pages, 5104 KiB  
Article
The Role of the Primary Cilium in Sensing Extracellular pH
by Kimberly F. Atkinson, Rinzhin T. Sherpa and Surya M. Nauli
Cells 2019, 8(7), 704; https://doi.org/10.3390/cells8070704 - 11 Jul 2019
Cited by 10 | Viewed by 4970
Abstract
Biosensors on the membrane of the vascular endothelium are responsible for sensing mechanical and chemical signals in the blood. Transduction of these stimuli into intracellular signaling cascades regulate cellular processes including ion transport, gene expression, cell proliferation, and/or cell death. The primary cilium [...] Read more.
Biosensors on the membrane of the vascular endothelium are responsible for sensing mechanical and chemical signals in the blood. Transduction of these stimuli into intracellular signaling cascades regulate cellular processes including ion transport, gene expression, cell proliferation, and/or cell death. The primary cilium is a well-known biosensor of shear stress but its role in sensing extracellular pH change has never been examined. As a cellular extension into the immediate microenvironment, the cilium could be a prospective sensor for changes in pH and regulator of acid response in cells. We aim to test our hypothesis that the primary cilium plays the role of an acid sensor in cells using vascular endothelial and embryonic fibroblast cells as in vitro models. We measure changes in cellular pH using pH-sensitive 2′,7′-biscarboxyethy1-5,6-carboxyfluorescein acetoxy-methylester (BCECF) fluorescence and mitogen-activated protein kinase (MAPK) activity to quantify responses to both extracellular pH (pHo) and intracellular pH (pHi) changes. Our studies show that changes in pHo affect pHi in both wild-type and cilia-less Tg737 cells and that the kinetics of the pHi response are similar in both cells. Acidic pHo or pHi was observed to change the length of primary cilia in wild-type cells while the cilia in Tg737 remained absent. Vascular endothelial cells respond to acidic pH through activation of ERK1/2 and p38-mediated signaling pathways. The cilia-less Tg737 cells exhibit delayed responsiveness to pHo dependent and independent pHi acidification as depicted in the phosphorylation profile of ERK1/2 and p38. Otherwise, intracellular pH homeostatic response to acidic pHo is similar between wild-type and Tg737 cells, indicating that the primary cilia may not be the sole sensor for physiological pH changes. These endothelial cells respond to pH changes with a predominantly K+-dependent pHi recovery mechanism, regardless of ciliary presence or absence. Full article
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10 pages, 1565 KiB  
Article
Ciliopathy-Associated Protein Kinase ICK Requires Its Non-Catalytic Carboxyl-Terminal Domain for Regulation of Ciliogenesis
by Yoon Seon Oh, Eric J. Wang, Casey D. Gailey, David L. Brautigan, Benjamin L. Allen and Zheng Fu
Cells 2019, 8(7), 677; https://doi.org/10.3390/cells8070677 - 04 Jul 2019
Cited by 18 | Viewed by 4063
Abstract
Loss-of-function mutations in the human ICK (intestinal cell kinase) gene cause dysfunctional primary cilia and perinatal lethality which are associated with human ciliopathies. The enzyme that we herein call CAPK (ciliopathy-associated protein kinase) is a serine/threonine protein kinase that has a highly conserved [...] Read more.
Loss-of-function mutations in the human ICK (intestinal cell kinase) gene cause dysfunctional primary cilia and perinatal lethality which are associated with human ciliopathies. The enzyme that we herein call CAPK (ciliopathy-associated protein kinase) is a serine/threonine protein kinase that has a highly conserved MAPK-like N-terminal catalytic domain and an unstructured C-terminal domain (CTD) whose functions are completely unknown. In this study, we demonstrate that truncation of the CTD impairs the ability of CAPK to interact with and phosphorylate its substrate, kinesin family member 3A (KIF3A). We also find that deletion of the CTD of CAPK compromises both localization to the primary cilium and negative regulation of ciliogenesis. Thus, CAPK substrate recognition, ciliary targeting, and ciliary function depend on the non-catalytic CTD of the protein which is predicted to be intrinsically disordered. Full article
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13 pages, 1700 KiB  
Article
Cyclic Nucleotide-Specific Optogenetics Highlights Compartmentalization of the Sperm Flagellum into cAMP Microdomains
by Diana N. Raju, Jan N. Hansen, Sebastian Rassmann, Birthe Stüven, Jan F. Jikeli, Timo Strünker, Heinz G. Körschen, Andreas Möglich and Dagmar Wachten
Cells 2019, 8(7), 648; https://doi.org/10.3390/cells8070648 - 27 Jun 2019
Cited by 13 | Viewed by 3622
Abstract
Inside the female genital tract, mammalian sperm undergo a maturation process called capacitation, which primes the sperm to navigate across the oviduct and fertilize the egg. Sperm capacitation and motility are controlled by 3′,5′-cyclic adenosine monophosphate (cAMP). Here, we show that optogenetics, the [...] Read more.
Inside the female genital tract, mammalian sperm undergo a maturation process called capacitation, which primes the sperm to navigate across the oviduct and fertilize the egg. Sperm capacitation and motility are controlled by 3′,5′-cyclic adenosine monophosphate (cAMP). Here, we show that optogenetics, the control of cellular signaling by genetically encoded light-activated proteins, allows to manipulate cAMP dynamics in sperm flagella and, thereby, sperm capacitation and motility by light. To this end, we used sperm that express the light-activated phosphodiesterase LAPD or the photo-activated adenylate cyclase bPAC. The control of cAMP by LAPD or bPAC combined with pharmacological interventions provides spatiotemporal precision and allows to probe the physiological function of cAMP compartmentalization in mammalian sperm. Full article
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11 pages, 6117 KiB  
Article
The Centriolar Adjunct–Appearance and Disassembly in Spermiogenesis and the Potential Impact on Fertility
by Anastasiia S. Garanina, Irina B. Alieva, Elizaveta E. Bragina, Emmanuelle Blanchard, Brigitte Arbeille, Fabrice Guerif, Svetlana Uzbekova and Rustem E. Uzbekov
Cells 2019, 8(2), 180; https://doi.org/10.3390/cells8020180 - 19 Feb 2019
Cited by 25 | Viewed by 3955
Abstract
During spermiogenesis, the proximal centriole forms a special microtubular structure: the centriolar adjunct. This structure appears at the spermatid stage, which is characterized by a condensed chromatin nucleus. We showed that the centriolar adjunct disappears completely in mature porcine spermatozoa. In humans, the [...] Read more.
During spermiogenesis, the proximal centriole forms a special microtubular structure: the centriolar adjunct. This structure appears at the spermatid stage, which is characterized by a condensed chromatin nucleus. We showed that the centriolar adjunct disappears completely in mature porcine spermatozoa. In humans, the centriolar adjunct remnants are present in a fraction of mature spermatids. For the first time, the structure of the centriolar adjunct in the cell, and its consequent impact on fertility, were examined. Ultrastructural analysis using transmission electron microscopy was performed on near 2000 spermatozoa per person, in two patients with idiopathic male sterility (IMS) and five healthy fertile donors. We measured the average length of the “proximal centriole + centriolar adjunct” complex in sections, where it had parallel orientation in the section plane, and found that it was significantly longer in the spermatozoa of IMS patients than in the spermatozoa of healthy donors. This difference was independent of chromatin condensation deficiency, which was also observed in the spermatozoa of IMS patients. We suggest that zygote arrest may be related to an incompletely disassembled centriolar adjunct in a mature spermatozoon. Therefore, centriolar adjunct length can be potentially used as a complementary criterion for the immaturity of spermatozoa in the diagnostics of IMS patients. Full article
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38 pages, 2325 KiB  
Review
Cilia Distal Domain: Diversity in Evolutionarily Conserved Structures
by Helena Soares, Bruno Carmona, Sofia Nolasco, Luís Viseu Melo and João Gonçalves
Cells 2019, 8(2), 160; https://doi.org/10.3390/cells8020160 - 14 Feb 2019
Cited by 25 | Viewed by 10710
Abstract
Eukaryotic cilia are microtubule-based organelles that protrude from the cell surface to fulfill sensory and motility functions. Their basic structure consists of an axoneme templated by a centriole/basal body. Striking differences in ciliary ultra-structures can be found at the ciliary base, the axoneme [...] Read more.
Eukaryotic cilia are microtubule-based organelles that protrude from the cell surface to fulfill sensory and motility functions. Their basic structure consists of an axoneme templated by a centriole/basal body. Striking differences in ciliary ultra-structures can be found at the ciliary base, the axoneme and the tip, not only throughout the eukaryotic tree of life, but within a single organism. Defects in cilia biogenesis and function are at the origin of human ciliopathies. This structural/functional diversity and its relationship with the etiology of these diseases is poorly understood. Some of the important events in cilia function occur at their distal domain, including cilia assembly/disassembly, IFT (intraflagellar transport) complexes’ remodeling, and signal detection/transduction. How axonemal microtubules end at this domain varies with distinct cilia types, originating different tip architectures. Additionally, they show a high degree of dynamic behavior and are able to respond to different stimuli. The existence of microtubule-capping structures (caps) in certain types of cilia contributes to this diversity. It has been proposed that caps play a role in axoneme length control and stabilization, but their roles are still poorly understood. Here, we review the current knowledge on cilia structure diversity with a focus on the cilia distal domain and caps and discuss how they affect cilia structure and function. Full article
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2018

Jump to: 2021, 2020, 2019

14 pages, 3579 KiB  
Article
SpermQ–A Simple Analysis Software to Comprehensively Study Flagellar Beating and Sperm Steering
by Jan N. Hansen, Sebastian Rassmann, Jan F. Jikeli and Dagmar Wachten
Cells 2019, 8(1), 10; https://doi.org/10.3390/cells8010010 - 26 Dec 2018
Cited by 40 | Viewed by 7209
Abstract
Motile cilia, also called flagella, are found across a broad range of species; some cilia propel prokaryotes and eukaryotic cells like sperm, while cilia on epithelial surfaces create complex fluid patterns e.g., in the brain or lung. For sperm, the picture has emerged [...] Read more.
Motile cilia, also called flagella, are found across a broad range of species; some cilia propel prokaryotes and eukaryotic cells like sperm, while cilia on epithelial surfaces create complex fluid patterns e.g., in the brain or lung. For sperm, the picture has emerged that the flagellum is not only a motor but also a sensor that detects stimuli from the environment, computing the beat pattern according to the sensory input. Thereby, the flagellum navigates sperm through the complex environment in the female genital tract. However, we know very little about how environmental signals change the flagellar beat and, thereby, the swimming behavior of sperm. It has been proposed that distinct signaling domains in the flagellum control the flagellar beat. However, a detailed analysis has been mainly hampered by the fact that current comprehensive analysis approaches rely on complex microscopy and analysis systems. Thus, knowledge on sperm signaling regulating the flagellar beat is based on custom quantification approaches that are limited to only a few aspects of the beat pattern, do not resolve the kinetics of the entire flagellum, rely on manual, qualitative descriptions, and are only a little comparable among each other. Here, we present SpermQ, a ready-to-use and comprehensive analysis software to quantify sperm motility. SpermQ provides a detailed quantification of the flagellar beat based on common time-lapse images acquired by dark-field or epi-fluorescence microscopy, making SpermQ widely applicable. We envision SpermQ becoming a standard tool in flagellar and motile cilia research that allows to readily link studies on individual signaling components in sperm and distinct flagellar beat patterns. Full article
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18 pages, 1288 KiB  
Review
The Roles of Primary Cilia in Cardiovascular Diseases
by Rajasekharreddy Pala, Maha Jamal, Qamar Alshammari and Surya M. Nauli
Cells 2018, 7(12), 233; https://doi.org/10.3390/cells7120233 - 27 Nov 2018
Cited by 38 | Viewed by 12604
Abstract
Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, [...] Read more.
Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, termed ciliopathies, with phenotypes ranging from polycystic kidney disease, liver disorders, mental retardation, and obesity to cardiovascular diseases. Primary cilia in vascular endothelia protrude into the lumen of blood vessels and function as molecular switches for calcium (Ca2+) and nitric oxide (NO) signaling. As mechanosensory organelles, endothelial cilia are involved in blood flow sensing. Dysfunction in endothelial cilia contributes to aberrant fluid-sensing and thus results in vascular disorders, including hypertension, aneurysm, and atherosclerosis. This review focuses on the most recent findings on the roles of endothelial primary cilia within vascular biology and alludes to the possibility of primary cilium as a therapeutic target for cardiovascular disorders. Full article
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12 pages, 930 KiB  
Review
Emerging Picture of Deuterosome-Dependent Centriole Amplification in MCCs
by Umama Shahid and Priyanka Singh
Cells 2018, 7(10), 152; https://doi.org/10.3390/cells7100152 - 27 Sep 2018
Cited by 17 | Viewed by 6353
Abstract
Multiciliated cells (MCCs) have several hair-like structures called cilia, which are required to propel substances on their surface. A cilium is organized from a basal body which resembles a hollow microtubule structure called a centriole. In terminally differentiated MCCs, hundreds of new basal [...] Read more.
Multiciliated cells (MCCs) have several hair-like structures called cilia, which are required to propel substances on their surface. A cilium is organized from a basal body which resembles a hollow microtubule structure called a centriole. In terminally differentiated MCCs, hundreds of new basal bodies/centrioles are formed via two parallel pathways: the centriole- and deuterosome-dependent pathways. The deuterosome-dependent pathway is also referred to as “de novo” because unlike the centriole-dependent pathway which requires pre-existing centrioles, in the de novo pathway multiple new centrioles are organized around non-microtubule structures called deuterosomes. In the last five years, some deuterosome-specific markers have been identified and concurrent advancements in the super-resolution techniques have significantly contributed to gaining insights about the major stages of centriole amplification during ciliogenesis. Altogether, a new picture is emerging which also challenges the previous notion that deuterosome pathway is de novo. This review is primarily focused on studies that have contributed towards the better understanding of deuterosome-dependent centriole amplification and presents a developing model about the major stages identified during this process. Full article
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15 pages, 4589 KiB  
Article
CFAP70 Is a Novel Axoneme-Binding Protein That Localizes at the Base of the Outer Dynein Arm and Regulates Ciliary Motility
by Noritoshi Shamoto, Keishi Narita, Tomohiro Kubo, Toshiyuki Oda and Sen Takeda
Cells 2018, 7(9), 124; https://doi.org/10.3390/cells7090124 - 29 Aug 2018
Cited by 31 | Viewed by 6428
Abstract
In the present study, we characterized CFAP70, a candidate of cilia-related protein in mice. As this protein has a cluster of tetratricopeptide repeat (TPR) domains like many components of the intraflagellar transport (IFT) complex, we investigated the domain functions of particular interest in [...] Read more.
In the present study, we characterized CFAP70, a candidate of cilia-related protein in mice. As this protein has a cluster of tetratricopeptide repeat (TPR) domains like many components of the intraflagellar transport (IFT) complex, we investigated the domain functions of particular interest in ciliary targeting and/or localization. RT-PCR and immunohistochemistry of various mouse tissues demonstrated the association of CFAP70 with motile cilia and flagella. A stepwise extraction of proteins from swine tracheal cilia showed that CFAP70 bound tightly to the ciliary axoneme. Fluorescence microscopy of the cultured ependyma expressing fragments of CFAP70 demonstrated that the N-terminus rather than the C-terminus with the TPR domains was more important for the ciliary localization. When CFAP70 was knocked down in cultured mouse ependyma, reductions in cilia beating frequency were observed. Consistent with these observations, a Chlamydomonas mutant lacking the CFAP70 homolog, FAP70, showed defects in outer dynein arm (ODA) activity and a reduction in flagellar motility. Cryo-electron tomography revealed that the N-terminus of FAP70 resided stably at the base of the ODA. These results demonstrated that CFAP70 is a novel regulatory component of the ODA in motile cilia and flagella, and that the N-terminus is important for its ciliary localization. Full article
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