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Open AccessArticle

Non-Overlapping Distributions and Functions of the VDAC Family in Ciliogenesis

by Shubhra Majumder, Ayla Cash and Harold A. Fisk

Cells 2015, 4(3), 331-353; https://doi.org/10.3390/cells4030331 - 31 Jul 2015

Cited by 13 | Viewed by 7461

Centrosomes are major microtubule-organizing centers of animal cells that consist of two centrioles. In mitotic cells, centrosomes are duplicated to serve as the poles of the mitotic spindle, while in quiescent cells, centrosomes move to the apical membrane where the oldest centriole is [...] Read more.

Centrosomes are major microtubule-organizing centers of animal cells that consist of two centrioles. In mitotic cells, centrosomes are duplicated to serve as the poles of the mitotic spindle, while in quiescent cells, centrosomes move to the apical membrane where the oldest centriole is transformed into a basal body to assemble a primary cilium. We recently showed that mitochondrial outer membrane porin VDAC3 localizes to centrosomes where it negatively regulates ciliogenesis. We show here that the other two family members, VDAC1 and VDAC2, best known for their function in mitochondrial bioenergetics, are also found at centrosomes. Like VDAC3, centrosomal VDAC1 is predominantly localized to the mother centriole, while VDAC2 localizes to centriolar satellites in a microtubule-dependent manner. Down-regulation of VDAC1 leads to inappropriate ciliogenesis, while its overexpression suppresses cilia formation, suggesting that VDAC1 and VDAC3 both negatively regulate ciliogenesis. However, this negative effect on ciliogenesis is not shared by VDAC2, which instead appears to promote maturation of primary cilia. Moreover, because overexpression of VDAC3 cannot compensate for depletion of VDAC1, our data suggest that while the entire VDAC family localizes to centrosomes, they have non-redundant functions in cilogenesis. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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Review

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2772 KiB

Open AccessReview

Airway Epithelial Cell Cilia and Obstructive Lung Disease

by Asma Yaghi and Myrna B. Dolovich

Cells 2016, 5(4), 40; https://doi.org/10.3390/cells5040040 - 11 Nov 2016

Cited by 104 | Viewed by 15449

Abstract

Airway epithelium is the first line of defense against exposure of the airway and lung to various inflammatory stimuli. Ciliary beating of airway epithelial cells constitutes an important part of the mucociliary transport apparatus. To be effective in transporting secretions out of the [...] Read more.

Airway epithelium is the first line of defense against exposure of the airway and lung to various inflammatory stimuli. Ciliary beating of airway epithelial cells constitutes an important part of the mucociliary transport apparatus. To be effective in transporting secretions out of the lung, the mucociliary transport apparatus must exhibit a cohesive beating of all ciliated epithelial cells that line the upper and lower respiratory tract. Cilia function can be modulated by exposures to endogenous and exogenous factors and by the viscosity of the mucus lining the epithelium. Cilia function is impaired in lung diseases such as COPD and asthma, and pharmacologic agents can modulate cilia function and mucus viscosity. Cilia beating is reduced in COPD, however, more research is needed to determine the structural-functional regulation of ciliary beating via all signaling pathways and how this might relate to the initiation or progression of obstructive lung diseases. Additionally, genotypes and how these can influence phenotypes and epithelial cell cilia function and structure should be taken into consideration in future investigations. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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Open AccessReview

The Trypanosome Flagellar Pocket Collar and Its Ring Forming Protein—TbBILBO1

by Doranda Perdomo, Mélanie Bonhivers and Derrick R. Robinson

Cells 2016, 5(1), 9; https://doi.org/10.3390/cells5010009 - 02 Mar 2016

Cited by 14 | Viewed by 7233

Abstract

Sub-species of Trypanosoma brucei are the causal agents of human African sleeping sickness and Nagana in domesticated livestock. These pathogens have developed an organelle-like compartment called the flagellar pocket (FP). The FP carries out endo- and exocytosis and is the only structure this [...] Read more.

Sub-species of Trypanosoma brucei are the causal agents of human African sleeping sickness and Nagana in domesticated livestock. These pathogens have developed an organelle-like compartment called the flagellar pocket (FP). The FP carries out endo- and exocytosis and is the only structure this parasite has evolved to do so. The FP is essential for parasite viability, making it an interesting structure to evaluate as a drug target, especially since it has an indispensible cytoskeleton component called the flagellar pocket collar (FPC). The FPC is located at the neck of the FP where the flagellum exits the cell. The FPC has a complex architecture and division cycle, but little is known concerning its organization. Recent work has focused on understanding how the FP and the FPC are formed and as a result of these studies an important calcium-binding, polymer-forming protein named TbBILBO1 was identified. Cellular biology analysis of TbBILBO1 has demonstrated its uniqueness as a FPC component and until recently, it was unknown what structural role it played in forming the FPC. This review summarizes the recent data on the polymer forming properties of TbBILBO1 and how these are correlated to the FP cytoskeleton. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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Open AccessReview

Cellular Mechanisms of Ciliary Length Control

by Jacob Keeling, Leonidas Tsiokas and Dipak Maskey

Cells 2016, 5(1), 6; https://doi.org/10.3390/cells5010006 - 29 Jan 2016

Cited by 64 | Viewed by 12289

Abstract

Cilia and flagella are evolutionarily conserved, membrane-bound, microtubule-based organelles on the surface of most eukaryotic cells. They play important roles in coordinating a variety of signaling pathways during growth, development, cell mobility, and tissue homeostasis. Defects in ciliary structure or function are associated [...] Read more.

Cilia and flagella are evolutionarily conserved, membrane-bound, microtubule-based organelles on the surface of most eukaryotic cells. They play important roles in coordinating a variety of signaling pathways during growth, development, cell mobility, and tissue homeostasis. Defects in ciliary structure or function are associated with multiple human disorders called ciliopathies. These diseases affect diverse tissues, including, but not limited to the eyes, kidneys, brain, and lungs. Many processes must be coordinated simultaneously in order to initiate ciliogenesis. These include cell cycle, vesicular trafficking, and axonemal extension. Centrioles play a central role in both cell cycle progression and ciliogenesis, making the transition between basal bodies and mitotic spindle organizers integral to both processes. The maturation of centrioles involves a functional shift from cell division toward cilium nucleation which takes place concurrently with its migration and fusion to the plasma membrane. Several proteinaceous structures of the distal appendages in mother centrioles are required for this docking process. Ciliary assembly and maintenance requires a precise balance between two indispensable processes; so called assembly and disassembly. The interplay between them determines the length of the resulting cilia. These processes require a highly conserved transport system to provide the necessary substances at the tips of the cilia and to recycle ciliary turnover products to the base using a based microtubule intraflagellar transport (IFT) system. In this review; we discuss the stages of ciliogenesis as well as mechanisms controlling the lengths of assembled cilia. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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1763 KiB

Open AccessReview

Form, Fabric, and Function of a Flagellum-Associated Cytoskeletal Structure

by Brooke Morriswood

Cells 2015, 4(4), 726-747; https://doi.org/10.3390/cells4040726 - 03 Nov 2015

Cited by 16 | Viewed by 10071

Abstract

Trypanosoma brucei is a uniflagellated protist and the causative agent of African trypanosomiasis, a neglected tropical disease. The single flagellum of T. brucei is essential to a number of cellular processes such as motility, and has been a longstanding focus of scientific enquiry. [...] Read more.

Trypanosoma brucei is a uniflagellated protist and the causative agent of African trypanosomiasis, a neglected tropical disease. The single flagellum of T. brucei is essential to a number of cellular processes such as motility, and has been a longstanding focus of scientific enquiry. A number of cytoskeletal structures are associated with the flagellum in T. brucei, and one such structure—a multiprotein complex containing the repeat motif protein TbMORN1—is the focus of this review. The TbMORN1-containing complex, which was discovered less than ten years ago, is essential for the viability of the mammalian-infective form of T. brucei. The complex has an unusual asymmetric morphology, and is coiled around the flagellum to form a hook shape. Proteomic analysis using the proximity-dependent biotin identification (BioID) technique has elucidated a number of its components. Recent work has uncovered a role for TbMORN1 in facilitating protein entry into the cell, thus providing a link between the cytoskeleton and the endomembrane system. This review summarises the extant data on the complex, highlights the outstanding questions for future enquiry, and provides speculation as to its possible role in a size-exclusion mechanism for regulating protein entry. The review additionally clarifies the nomenclature associated with this topic, and proposes the adoption of the term “hook complex” to replace the former name “bilobe” to describe the complex. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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Open AccessReview

Photoreceptor Sensory Cilium: Traversing the Ciliary Gate

by Hemant Khanna

Cells 2015, 4(4), 674-686; https://doi.org/10.3390/cells4040674 - 15 Oct 2015

Cited by 43 | Viewed by 14216

Abstract

Cilia are antenna-like extensions of the plasma membrane found in nearly all cell types. In the retina of the eye, photoreceptors develop unique sensory cilia. Not much was known about the mechanisms underlying the formation and function of photoreceptor cilia, largely because of [...] Read more.

Cilia are antenna-like extensions of the plasma membrane found in nearly all cell types. In the retina of the eye, photoreceptors develop unique sensory cilia. Not much was known about the mechanisms underlying the formation and function of photoreceptor cilia, largely because of technical limitations and the specific structural and functional modifications that cannot be modeled in vitro. With recent advances in microscopy techniques and molecular and biochemical approaches, we are now beginning to understand the molecular basis of photoreceptor ciliary architecture, ciliary function and its involvement in human diseases. Here, I will discuss the studies that have revealed new knowledge of how photoreceptor cilia regulate their identity and function while coping with high metabolic and trafficking demands associated with processing light signal. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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3816 KiB

Open AccessReview

Specialized Cilia in Mammalian Sensory Systems

by Nathalie Falk, Marlene Lösl, Nadja Schröder and Andreas Gießl

Cells 2015, 4(3), 500-519; https://doi.org/10.3390/cells4030500 - 11 Sep 2015

Cited by 79 | Viewed by 15297

Abstract

Cilia and flagella are highly conserved and important microtubule-based organelles that project from the surface of eukaryotic cells and act as antennae to sense extracellular signals. Moreover, cilia have emerged as key players in numerous physiological, developmental, and sensory processes such as hearing, [...] Read more.

Cilia and flagella are highly conserved and important microtubule-based organelles that project from the surface of eukaryotic cells and act as antennae to sense extracellular signals. Moreover, cilia have emerged as key players in numerous physiological, developmental, and sensory processes such as hearing, olfaction, and photoreception. Genetic defects in ciliary proteins responsible for cilia formation, maintenance, or function underlie a wide array of human diseases like deafness, anosmia, and retinal degeneration in sensory systems. Impairment of more than one sensory organ results in numerous syndromic ciliary disorders like the autosomal recessive genetic diseases Bardet-Biedl and Usher syndrome. Here we describe the structure and distinct functional roles of cilia in sensory organs like the inner ear, the olfactory epithelium, and the retina of the mouse. The spectrum of ciliary function in fundamental cellular processes highlights the importance of elucidating ciliopathy-related proteins in order to find novel potential therapies. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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Open AccessReview

Ciliary/Flagellar Protein Ubiquitination

by Huan Long, Qiyu Wang and Kaiyao Huang

Cells 2015, 4(3), 474-482; https://doi.org/10.3390/cells4030474 - 02 Sep 2015

Cited by 12 | Viewed by 8156

Abstract

Cilia/flagella are conserved eukaryotic organelles that play an important role in the control of cell motility and detection of environmental cues. However, the molecular mechanisms underlying ciliary/flagellar assembly, maintenance, disassembly, and signal transduction are not yet completely understood. Recent studies demonstrated that post-translational [...] Read more.

Cilia/flagella are conserved eukaryotic organelles that play an important role in the control of cell motility and detection of environmental cues. However, the molecular mechanisms underlying ciliary/flagellar assembly, maintenance, disassembly, and signal transduction are not yet completely understood. Recent studies demonstrated that post-translational modifications (PTMs) such as phosphorylation, methylation, glutamylation, and ubiquitination are involved in these processes. In this mini review, we present a summary of research progress in ciliary/flagellar protein ubiquitination, including the ubiquitin conjugation system identified by proteomics as well as the role of ciliary/flagellar protein ubiquitination in flagellar disassembly, motility, and signal transduction. Moreover, we described putative further research directions in the study of ciliary/flagellar protein ubiquitination. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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Open AccessReview

Cyclic GMP and Cilia Motility

by Todd A. Wyatt

Cells 2015, 4(3), 315-330; https://doi.org/10.3390/cells4030315 - 31 Jul 2015

Cited by 14 | Viewed by 7498

Abstract

Motile cilia of the lungs respond to environmental challenges by increasing their ciliary beat frequency in order to enhance mucociliary clearance as a fundamental tenant of innate defense. One important second messenger in transducing the regulable nature of motile cilia is cyclic guanosine [...] Read more.

Motile cilia of the lungs respond to environmental challenges by increasing their ciliary beat frequency in order to enhance mucociliary clearance as a fundamental tenant of innate defense. One important second messenger in transducing the regulable nature of motile cilia is cyclic guanosine 3′,5′-monophosphate (cGMP). In this review, the history of cGMP action is presented and a survey of the existing data addressing cGMP action in ciliary motility is presented. Nitric oxide (NO)-mediated regulation of cGMP in ciliated cells is presented in the context of alcohol-induced cilia function and dysfunction. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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Open AccessReview

Novel Insights into the Development and Function of Cilia Using the Advantages of the Paramecium Cell and Its Many Cilia

by Junji Yano, Megan S. Valentine and Judith L. Van Houten

Cells 2015, 4(3), 297-314; https://doi.org/10.3390/cells4030297 - 29 Jul 2015

Cited by 12 | Viewed by 10373

Abstract

Paramecium species, especially P. tetraurelia and caudatum, are model organisms for modern research into the form and function of cilia. In this review, we focus on the ciliary ion channels and other transmembrane proteins that control the beat frequency and wave form [...] Read more.

Paramecium species, especially P. tetraurelia and caudatum, are model organisms for modern research into the form and function of cilia. In this review, we focus on the ciliary ion channels and other transmembrane proteins that control the beat frequency and wave form of the cilium by controlling the signaling within the cilium. We put these discussions in the context of the advantages that Paramecium brings to the understanding of ciliary motility: mutants for genetic dissections of swimming behavior, electrophysiology, structural analysis, abundant cilia for biochemistry and modern proteomics, genomics and molecular biology. We review the connection between behavior and physiology, which allows the cells to broadcast the function of their ciliary channels in real time. We build a case for the important insights and advantages that this model organism continues to bring to the study of cilia. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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Open AccessReview

The Possible Roles of the Dentate Granule Cell’s Leptin and Other Ciliary Receptors in Alzheimer’s Neuropathology

by James F. Whitfield, Anna Chiarini, Ilaria Dal Prà, Ubaldo Armato and Balu Chakravarthy

Cells 2015, 4(3), 253-274; https://doi.org/10.3390/cells4030253 - 13 Jul 2015

Cited by 5 | Viewed by 7694

Abstract

Dentate-gyral granule cells in the hippocampus plus dentate gyrus memory-recording/retrieving machine, unlike most other neurons in the brain, are continuously being generated in the adult brain with the important task of separating overlapping patterns of data streaming in from the outside world via [...] Read more.

Dentate-gyral granule cells in the hippocampus plus dentate gyrus memory-recording/retrieving machine, unlike most other neurons in the brain, are continuously being generated in the adult brain with the important task of separating overlapping patterns of data streaming in from the outside world via the entorhinal cortex. This “adult neurogenesis” is driven by tools in the mature granule cell’s cilium. Here we report our discovery of leptin’s LepRb receptor in this cilium. In addition, we discuss how ciliary LepRb signaling might be involved with ciliary p75^NTR and SSTR3 receptors in adult neurogenesis and memory formation as well as attenuation of Alzheimer’s neuropathology by reducing the production of its toxic amyloid-β-derived drivers. Full article

(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)

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