Progress in ciliary ion channel physiology

Mammalian cilia are ubiquitous appendages found on the apical surface of cells. Primary and motile cilia are distinct in both morphology and function. Most cells have a solitary primary cilium (9+0), which lacks the central microtubule doublet characteristic of motile cilia (9+2). The immotile primary cilia house unique signaling components and sequester several important transcription factors. In contrast, motile cilia commonly extend into the lumen of respiratory airways, fallopian tubes, and brain ventricles to move their contents and/or produce gradients. In this review, we focus on the composition of putative ion channels found in both types of cilia and in the periciliary membrane and discuss their proposed functions. Our discussion does not cover specialized cilia in photoreceptor or olfactory cells, which express many more ion channels.

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Tau tubulin kinase is required for spermatogenesis and development of motile cilia in planarian flatworms

Molecular Biology of the Cell ◽

10.1091/mbc.e18-10-0663 ◽

2019 ◽

Vol 30 (17) ◽

pp. 2155-2170 ◽

Cited By ~ 3

Author(s):

Robert Alan Magley ◽

Labib Rouhana

Keyword(s):

Intracellular Signaling ◽

Primary Cilia ◽

Testicular Tissue ◽

Structural Defects ◽

Apical Surface ◽

Transmission Electron ◽

Sperm Development ◽

Associated Proteins ◽

Motile Cilia ◽

Reproductive Processes

Cilia are microtubule-based structures that protrude from the apical surface of cells to mediate motility, transport, intracellular signaling, and environmental sensing. Tau tubulin kinases (TTBKs) destabilize microtubules by phosphorylating microtubule-associated proteins (MAPs) of the MAP2/Tau family, but also contribute to the assembly of primary cilia during embryogenesis. Expression of TTBKs is enriched in testicular tissue, but their relevance to reproductive processes is unknown. We identified six TTBK homologues in the genome of the planarian Schmidtea mediterranea ( Smed-TTBK-a, -b, -c, -d, -e, and -f), all of which are preferentially expressed in testes. Inhibition of TTBK paralogues by RNA interference (RNAi) revealed a specific requirement for Smed-TTBK-d in postmeiotic regulation of spermatogenesis. Disrupting expression of Smed-TTBK-d results in loss of spermatozoa, but not spermatids. In the soma, Smed-TTBK-d RNAi impaired the function of multiciliated epidermal cells in propelling planarian movement, as well as the osmoregulatory function of protonephridia. Decreased density and structural defects of motile cilia were observed in the epidermis of Smed-TTBK-d(RNAi) by phase contrast, immunofluorescence, and transmission electron microscopy. Altogether, these results demonstrate that members of the TTBK family of proteins are postmeiotic regulators of sperm development and also contribute to the formation of motile cilia in the soma.

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Ultrastructural evidence for an unusual mode of ciliogenesis in mouse multiciliated epithelia

Microscopy ◽

10.1093/jmicro/dfaa074 ◽

2020 ◽

Author(s):

Keishi Narita ◽

Sen Takeda

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Primary Cilia ◽

Single Cells ◽

Wild Type Mouse ◽

Wild Type ◽

Brain Ventricles ◽

Ultrastructural Evidence ◽

Transmission Electron ◽

Motile Cilia

Abstract Multiciliogenesis is a cascading process for generating hundreds of motile cilia in single cells. In vertebrates, this process has been investigated in the ependyma of brain ventricles and the ciliated epithelia of the airway and oviduct. Although the early steps to amplify centrioles have been characterized in molecular detail, subsequent steps to establish multicilia have been relatively overlooked. Here, we focused on unusual cilia-related structures previously observed in wild-type mouse ependyma using transmission electron microscopy and analyzed their ultrastructural features and the frequency of their occurrence. In the ependyma, $\sim$5% of cilia existed as bundles; while the majority of the bundles were paired, bundles of more than three cilia were also found. Furthermore, apical protrusions harboring multiple sets of axonemes were occasionally observed (0–2 per section), suggesting an unusual mode of ciliogenesis. In trachea and oviduct epithelia, ciliary bundles were absent, but protrusions containing multiple axonemes were observed. At the base of such protrusions, certain axonemes were completely enwrapped by membranes, whereas others remained incompletely enwrapped. These data suggested that the late steps of multiciliogenesis might include a unique process underlying the development of cilia, which is distinct from the ciliogenesis of primary cilia.

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Polycystic Diseases in Visceral Organs

Obstetrics and Gynecology International ◽

10.1155/2011/609370 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Shakila Abdul-Majeed ◽

Surya M. Nauli

Keyword(s):

Mammalian Cells ◽

Primary Cilia ◽

Polycystic Ovarian Syndrome ◽

Cyst Formation ◽

Apical Surface ◽

Polycystic Kidney ◽

Pancreas Disease ◽

Polycystic Liver ◽

And Function ◽

Ovarian Syndrome

Primary cilia are nonmotile, microtubule-based, antenna-like organelles projecting from the apical surface of most mammalian cells. Elegant studies have established the importance of ciliary structure and function in signal transduction and the sensory roles of cilia in maintaining healthy cellular state. In particular, dysfunctional cilia have been implicated in a large number of diseases mainly characterized by the presence of fluid-filled cysts in various organs. Aside from polycystic kidney disease (PKD), however, the roles of cilia in polycystic liver disease (PLD), polycystic pancreas disease (PPD), and polycystic ovarian syndrome (PCOS) are still very vague. In addition, although gender and sex hormones are known to regulate cyst formation, their roles in regulating physiological functions of cilia need to be further explored.

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Signaling the differences between cilia

eLife ◽

10.7554/elife.12760 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 2

Author(s):

Polina Lishko ◽

Yuriy Kirichok

Keyword(s):

Ion Channels ◽

Calcium Ion ◽

Primary Cilia ◽

Calcium Ion Channels ◽

Motile Cilia ◽

Cilia And Flagella

Calcium ion channels that determine many of the properties of cilia are different in motile cilia as compared to primary cilia and flagella.

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PDGFRα: Expression and Function during Mitral Valve Morphogenesis

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8030028 ◽

2021 ◽

Vol 8 (3) ◽

pp. 28

Author(s):

Kelsey Moore ◽

Diana Fulmer ◽

Lilong Guo ◽

Natalie Koren ◽

Janiece Glover ◽

...

Keyword(s):

Mitral Valve ◽

Primary Cilia ◽

Growth Factor Receptor ◽

Akt Phosphorylation ◽

Valve Development ◽

Biochemical Assays ◽

Factor Receptor Alpha ◽

Mesenchymal Transformation ◽

And Function

Mitral valve prolapse (MVP) is a common form of valve disease and can lead to serious secondary complications. The recent identification of MVP causal mutations in primary cilia-related genes has prompted the investigation of cilia-mediated mechanisms of disease inception. Here, we investigate the role of platelet-derived growth factor receptor-alpha (PDGFRα), a receptor known to be present on the primary cilium, during valve development using genetically modified mice, biochemical assays, and high-resolution microscopy. While PDGFRα is expressed throughout the ciliated valve interstitium early in development, its expression becomes restricted on the valve endocardium by birth and through adulthood. Conditional ablation of Pdgfra with Nfatc1-enhancer Cre led to significantly enlarged and hypercellular anterior leaflets with disrupted endothelial adhesions, activated ERK1/2, and a dysregulated extracellular matrix. In vitro culture experiments confirmed a role in suppressing ERK1/2 activation while promoting AKT phosphorylation. These data suggest that PDGFRα functions to suppress mesenchymal transformation and disease phenotypes by stabilizing the valve endocardium through an AKT/ERK pathway.

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Kinematic Design of Functional Nanoscale Mechanisms From Molecular Primitives

Journal of Micro and Nano-Manufacturing ◽

10.1115/1.4051472 ◽

2021 ◽

Author(s):

Meysam T. Chorsi ◽

Pouya Tavousi ◽

Caitlyn Mundrane ◽

Vitaliy Gorbatyuk ◽

Kazem Kazerounian ◽

...

Keyword(s):

Ion Channels ◽

Range Of Motion ◽

Systematic Approach ◽

Design Space ◽

Vital Role ◽

Degree Of Freedom ◽

Living Systems ◽

Kinematic Design ◽

Systematic Exploration ◽

And Function

Abstract Natural nanomechanisms such as capillaries, neurotransmitters, and ion channels play a vital role in the living systems. But the design principles developed by nature through evolution are not well understood and, hence, not applicable to engineered nanomachines. Thus, the design of nanoscale mechanisms with prescribed functions remains a challenge. Here, we present a systematic approach based on established kinematics techniques to designing, analyzing, and controlling manufacturable nanomachines with prescribed mobility and function built from a finite but extendable number of available "molecular primitives." Our framework allows the systematic exploration of the design space of irreducibly simple nanomachines, built with prescribed motion specification by combining available nanocomponents into systems having constrained, and consequently controllable motions. We show that the proposed framework has allowed us to discover and verify a molecule in the form of a seven link, seven revolute (7R) close loop spatial linkage with mobility (degree of freedom) of one. Furthermore, our experiments exhibit the type and range of motion predicted by our simulations. Enhancing such a structure into functional nanomechanisms by exploiting and controlling their motions individually or as part of an ensemble could galvanize development of the multitude of engineering, scientific, medical, and consumer applications that can benefit from engineered nanomachines.

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Polaris, a protein disrupted inorpkmutant mice, is required for assembly of renal cilium

AJP Renal Physiology ◽

10.1152/ajprenal.00273.2001 ◽

2002 ◽

Vol 282 (3) ◽

pp. F541-F552 ◽

Cited By ~ 169

Author(s):

Bradley K. Yoder ◽

Albert Tousson ◽

Leigh Millican ◽

John H. Wu ◽

Charles E. Bugg ◽

...

Keyword(s):

Primary Cilia ◽

Collecting Duct ◽

Physiological Role ◽

Duct Cell ◽

Cystic Kidney Disease ◽

Cystic Kidney ◽

Apical Surface ◽

Cystic Disease ◽

Cortical Collecting Duct

Cilia are organelles that play diverse roles, from fluid movement to sensory reception. Polaris, a protein associated with cystic kidney disease in Tg737°rpkmice, functions in a ciliogenic pathway. Here, we explore the role of polaris in primary cilia on Madin-Darby canine kidney cells. The results indicate that polaris localization and solubility change dramatically during cilia formation. These changes correlate with the formation of basal bodies and large protein rafts at the apical surface of the epithelia. A cortical collecting duct cell line has been derived from mice with a mutation in the Tg737 gene. These cells do not develop normal cilia, which can be corrected by reexpression of the wild-type Tg737 gene. These data suggest that the primary cilia are important for normal renal function and/or development and that the ciliary defect may be a contributing factor to the cystic disease in Tg737°rpkmice. Further characterization of these cells will be important in elucidating the physiological role of renal cilia and in determining their relationship to cystic disease.

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