The establishment of rotational polarity in the airway and ependymal cilia: analysis with a novel cilium motility mutant mouse

2013 ◽  
Vol 304 (11) ◽  
pp. L736-L745 ◽  
Author(s):  
Moe Matsuo ◽  
Atsuko Shimada ◽  
Sumito Koshida ◽  
Yumiko Saga ◽  
Hiroyuki Takeda
Keyword(s):  
Essential Feature ◽  
Ependymal Cells ◽  
Chronic Respiratory Diseases ◽  
Ciliary Motility ◽  
Motility Mutant ◽  
Axonemal Dynein ◽  
Airway Cilia ◽  
Ependymal Cilia ◽  
Basal Foot

The airway is covered by multicilia that beat in a metachronous manner toward the mouth to eliminate debris and infectious particles. Coordinated one-directional beating is an essential feature of multicilia in the airway to guarantee proper mucociliary clearance. Defects in ciliary motility lead to primary ciliary dyskinesia (PCD), with major symptoms including bronchitis and other chronic respiratory diseases. Recent work suggested that ciliary motility and planar polarity are required in the process of ciliary alignment that produces coordinated beating. However, the extent to which cilia motility is involved in this process in mammals has not yet been fully clarified. Here, to address the role of ciliary motility in the process of coordinated ciliary alignment, we analyzed Kintoun mice mutants ( Ktu−/−). Ktu−/− exhibited typical phenotypes of PCD with complete loss of ciliary motility in trachea and another ciliated tissue, the brain ependyma. Immunohistochemistry using antibodies against axonemal dynein confirmed the loss of multiple axonemal dynein components in mutant cilia. Observation of cilia orientation based on basal foot directions revealed that ciliary motility was not required in the alignment of airway cilia, whereas a strong requirement was observed in brain ependymal cells. Thus we conclude that the involvement of ciliary motility in the establishment of coordinated ciliary alignment varies among tissues.

scholarly journals The molecular dynamics of subdistal appendages in multi-ciliated cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hyunchul Ryu ◽  
Haeryung Lee ◽  
Jiyeon Lee ◽  
Hyuna Noh ◽  
Miram Shin ◽  
...  
Keyword(s):  
Basal Body ◽  
Ependymal Cells ◽  
Basal Bodies ◽  
Ciliary Beating ◽  
Sam Domain ◽  
Adult Mice ◽  
Region I ◽  
Evolutionarily Conserved ◽  
Basal Foot

AbstractThe motile cilia of ependymal cells coordinate their beats to facilitate a forceful and directed flow of cerebrospinal fluid (CSF). Each cilium originates from a basal body with a basal foot protruding from one side. A uniform alignment of these basal feet is crucial for the coordination of ciliary beating. The process by which the basal foot originates from subdistal appendages of the basal body, however, is unresolved. Here, we show FGFR1 Oncogene Partner (FOP) is a useful marker for delineating the transformation of a circular, unpolarized subdistal appendage into a polarized structure with a basal foot. Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A) interacts with FOP to assemble region I of the basal foot. Importantly, disruption of ANKS1A reduces the size of region I. This produces an unstable basal foot, which disrupts rotational polarity and the coordinated beating of cilia in young adult mice. ANKS1A deficiency also leads to severe degeneration of the basal foot in aged mice and the detachment of cilia from their basal bodies. This role of ANKS1A in the polarization of the basal foot is evolutionarily conserved in vertebrates. Thus, ANKS1A regulates FOP to build and maintain the polarity of subdistal appendages.

From Genesis To Revelation: The Role Of Inflammatory Mediators In Chronic Respiratory Diseases And Their Control By Nucleic Acid-Based Drugs

2016 ◽  
Vol 13 (999) ◽  
pp. 1-1 ◽  
Author(s):  
Sante Di Gioia ◽  
Carla Sardo ◽  
Stefano Castellani ◽  
Barbara Porsio ◽  
Giuliana Belgiovine ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Inflammatory Mediators ◽  
Respiratory Diseases ◽  
Chronic Respiratory Diseases

scholarly journals Differential Role of PTEN Phosphatase in Chemotactic Growth Cone Guidance

2013 ◽  
Vol 288 (29) ◽  
pp. 20837-20842 ◽  
Author(s):  
Steven J. Henle ◽  
Lucas P. Carlstrom ◽  
Thomas R. Cheever ◽  
John R. Henley
Keyword(s):  
Growth Cone ◽  
Essential Feature ◽  
Pten Expression ◽  
Spinal Neurons ◽  
Phosphoinositide Phosphatase ◽  
Integrin Clustering ◽  
Myelin Associated Glycoprotein ◽  
Phosphatase And Tensin Homologue ◽  
Regenerative Therapies

Negatively targeting the tumor suppressor and phosphoinositide phosphatase PTEN (phosphatase and tensin homologue) promotes axon regrowth after injury. How PTEN functions in axon guidance has remained unknown. Here we report the differential role of PTEN in chemotactic guidance of axonal growth cones. Down-regulating PTEN expression in Xenopus laevis spinal neurons selectively abolished growth cone chemorepulsion but permitted chemoattraction. These findings persisted during cAMP-dependent switching of turning behaviors. Live cell imaging using a GFP biosensor revealed rapid PTEN-dependent depression of phosphatidylinositol 3,4,5-trisphosphate levels in the growth cone induced by the repellent myelin-associated glycoprotein. Moreover, down-regulating PTEN expression blocked negative remodeling of β1-integrin adhesions triggered by myelin-associated glycoprotein, yet permitted integrin clustering by a positive chemotropic treatment. Thus, PTEN negatively regulates growth cone phosphatidylinositol 3,4,5-trisphosphate levels and mediates chemorepulsion, whereas chemoattraction is PTEN-independent. Regenerative therapies targeting PTEN may therefore suppress growth cone repulsion to soluble cues while permitting attractive guidance, an essential feature for re-forming functional neural circuits.

scholarly journals Nucleases as molecular targets for cancer diagnosis

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alien Balian ◽  
Frank J. Hernandez
Keyword(s):  
Enzymatic Activity ◽  
Cancer Diagnosis ◽  
Essential Feature ◽  
Treatment Options ◽  
Cancer Biomarkers ◽  
Diagnostic Biomarkers ◽  
Early Cancer Diagnosis ◽  
Novel Biomarkers ◽  
Made In

AbstractEarly cancer diagnosis is a crucial element to improved treatment options and survival. Great research efforts have been made in the search for better performing cancer diagnostic biomarkers. However, the quest continues as novel biomarkers with high accuracy for an early diagnosis remain an unmet clinical need. Nucleases, which are enzymes capable of cleaving nucleic acids, have been long considered as potential cancer biomarkers. The implications of nucleases are key for biological functions, their presence in different cellular counterparts and catalytic activity led the enthusiasm towards investigating the role of nucleases as promising cancer biomarkers. However, the most essential feature of these proteins, which is their enzymatic activity, has not been fully exploited. This review discusses nucleases interrogated as cancer biomarkers, providing a glimpse of their physiological roles. Moreover, it highlights the potential of harnessing the enzymatic activity of cancer-associated nucleases as a novel diagnostic biomarker using nucleic acid probes as substrates.

scholarly journals PACRG and FAP20 form the inner junction of axonemal doublet microtubules and regulate ciliary motility

2019 ◽  
Vol 30 (15) ◽  
pp. 1805-1816 ◽  
Author(s):  
Erin E. Dymek ◽  
Jianfeng Lin ◽  
Gang Fu ◽  
Mary E. Porter ◽  
Daniela Nicastro ◽  
...  
Keyword(s):  
Cell Motility ◽  
Electron Tomography ◽  
Structural Studies ◽  
Ciliary Beating ◽  
Ciliary Motility ◽  
Functional Studies ◽  
Cryo Electron Tomography ◽  
Motile Cilia

We previously demonstrated that PACRG plays a role in regulating dynein-driven microtubule sliding in motile cilia. To expand our understanding of the role of PACRG in ciliary assembly and motility, we used a combination of functional and structural studies, including newly identified Chlamydomonas pacrg mutants. Using cryo-electron tomography we show that PACRG and FAP20 form the inner junction between the A- and B-tubule along the length of all nine ciliary doublet microtubules. The lack of PACRG and FAP20 also results in reduced assembly of inner-arm dynein IDA b and the beak-MIP structures. In addition, our functional studies reveal that loss of PACRG and/or FAP20 causes severe cell motility defects and reduced in vitro microtubule sliding velocities. Interestingly, the addition of exogenous PACRG and/or FAP20 protein to isolated mutant axonemes restores microtubule sliding velocities, but not ciliary beating. Taken together, these studies show that PACRG and FAP20 comprise the inner junction bridge that serves as a hub for both directly modulating dynein-driven microtubule sliding, as well as for the assembly of additional ciliary components that play essential roles in generating coordinated ciliary beating.

scholarly journals Carcinogenesis and Chemotherapy Viewed from the Perspective of Stoichiometric Network Analysis (SNA): What Can the Biological System of the Elements Contribute to an Understanding of Tumour Induction by Elemental Chemical Noxae (e.g., Ni2+, Cd2+) and to an Understanding of Chemotherapy?

2003 ◽  
Vol 3 ◽  
pp. 319-341 ◽  
Author(s):  
Stefan Franzle ◽  
Bernd Markert
Keyword(s):  
Network Analysis ◽  
Biological System ◽  
Cell Biology ◽  
Essential Feature ◽  
Comprehensive Treatment ◽  
Biological Processes ◽  
Tumour Induction ◽  
Stoichiometric Network Analysis ◽  
Autocatalytic Networks

The biological application of stoichiometric network analysis (SNA) permits an understanding of tumour induction, carcinogenesis, and chemotherapy. Starting from the Biological System of the Elements, which provides a comprehensive treatment of the functions and distributions of chemical (trace) elements in biology, an attempt is made to interrelate the essential feature of biology and — regrettably — of tumour genesis by superimposing SNA reasoning on common features of all crucial biological processes. For this purpose, aspects, effects and drawbacks of autocatalysis (identical reproduction which can occur either under control or without control [in tumours]) are linked with the known facts about element distributions in living beings and about interference of metals with tumours (in terms of both chemotherapy and carcinogenesis). The essential role of autocatalysis in biology and the drawbacks of either controlled or spontaneous cell division can be used to understand crucial aspects of carcinogenesis and chemotherapy because SNA describes and predicts effects of autocatalysis, including phase effects that may be due to some kind of intervention. The SNA-based classifications of autocatalytic networks in cell biology are outlined here to identify new approaches to chemotherapy.

scholarly journals Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland

2017 ◽  
Vol 114 (31) ◽  
pp. 8408-8413 ◽  
Author(s):  
Cristina Sáenz de Miera ◽  
Béatrice Bothorel ◽  
Catherine Jaeger ◽  
Valérie Simonneaux ◽  
David Hazlerigg
Keyword(s):  
Pituitary Gland ◽  
Thyroid Stimulating Hormone ◽  
Day Length ◽  
Ependymal Cells ◽  
Pars Tuberalis ◽  
Phenotypic Flexibility ◽  
Calendar Time ◽  
Wild Mammals ◽  
Melatonin Production

In wild mammals, offspring development must anticipate forthcoming metabolic demands and opportunities. Within species, different developmental strategies may be used, dependent on when in the year conception takes place. This phenotypic flexibility is initiated before birth and is linked to the pattern of day length (photoperiod) exposure experienced by the mother during pregnancy. This programming depends on transplacental communication via the pineal hormone melatonin. Here, we show that, in the Siberian hamster (Phodopus sungorus), the programming effect of melatonin is mediated by the pars tuberalis (PT) of the fetal pituitary gland, before the fetal circadian system and autonomous melatonin production is established. Maternal melatonin acts on the fetal PT to control expression of thyroid hormone deiodinases in ependymal cells (tanycytes) of the fetal hypothalamus, and hence neuroendocrine output. This mechanism sets the trajectory of reproductive and metabolic development in pups and has a persistent effect on their subsequent sensitivity to the photoperiod. This programming effect depends on tanycyte sensitivity to thyroid stimulating hormone (TSH), which is dramatically and persistently increased by short photoperiod exposure in utero. Our results define the role of the fetal PT in developmental programming of brain function by maternal melatonin and establish TSH signal transduction as a key substrate for the encoding of internal calendar time from birth to puberty.

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