scholarly journals How signals of calcium ions initiate the beats of cilia and flagella

2019 ◽  
Author(s):  
M. V. Satarić ◽  
T. Nemeš ◽  
D. Sekulić ◽  
J. A. Tuszynski
Keyword(s):  
Atp Hydrolysis ◽  
Cellular Motility ◽  
Cell Organelles ◽  
Ciliary Movement ◽  
Ciliary Function ◽  
Dynein Motor ◽  
Combined Action ◽  
Axonemal Dynein ◽  
Cilia And Flagella

ABSTRACTCilia and flagella are cell organelles serving basic roles in cellular motility. Ciliary movement is performed by a sweeping-like repeated bending motion, which gives rise to a self-propagating “ciliary beat”. The hallmark structure in cilia is the axoneme, a stable architecture of microtubule doublets. The motion of axoneme is powered by the axonemal dynein motor family powered by ATP hydrolysis. It is still unclear how the organized beat of cilium and flagella emerges from the combined action of hundreds of dynein molecules. It has been hypothesized that such coordination is mediated by mechanical stress due to transverse, radial or sliding deformations. The beating asymmetry is crucial for airway ciliary function and it requires tubulin glutamination a unique posttranslational modification of C-termini of constituent microtubules that is highly abundant in cilia and flagella. The exact role of tubulin glutamination in ciliary or flagellar function is still unclear. Here we examine the role of calcium (Ca2+) ions based on the experimental evidences that the flagellar asymmetry can be increased due to the entry of extracellular Ca2+through, for example, nimodipine-sensitive pathway located in the flagella. We propose a new scenario based on the polyelectrolyte properties of cellular microtubules (MTs) such that dynamic influx of Ca2+ions provides the initiation and synchronization of dynein sliding along microtubules. We also point out the possible interplay between tubulin polyglutaminated C-termini and localized pulses of Ca2+ions along microtubules.

scholarly journals Force-Generating Mechanism of Axonemal Dynein in Solo and Ensemble

2020 ◽  
Vol 21 (8) ◽  
pp. 2843
Author(s):  
Kenta Ishibashi ◽  
Hitoshi Sakakibara ◽  
Kazuhiro Oiwa
Keyword(s):  
Single Molecule ◽  
Conformational Changes ◽  
Atp Hydrolysis ◽  
Current Knowledge ◽  
Expression System ◽  
Molecular Architecture ◽  
Electron Microscopic ◽  
Axonemal Dynein ◽  
Cilia And Flagella ◽  
Amount Of Knowledge

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.

scholarly journals CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Gerard W. Dougherty ◽  
Katsutoshi Mizuno ◽  
Tabea Nöthe-Menchen ◽  
Yayoi Ikawa ◽  
Karsten Boldt ◽  
...  
Keyword(s):  
Atp Hydrolysis ◽  
Adenine Nucleotide ◽  
Adenosine Monophosphate ◽  
Adenosine Diphosphate ◽  
Situs Inversus Totalis ◽  
Proteomic Profiling ◽  
Binding Interface ◽  
Axonemal Dynein ◽  
Cilia And Flagella

Abstract Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45−/− mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module.

scholarly journals Nonlinear amplitude dynamics in flagellar beating

2017 ◽  
Vol 4 (3) ◽  
pp. 160698 ◽  
Author(s):  
David Oriola ◽  
Hermes Gadêlha ◽  
Jaume Casademunt
Keyword(s):  
Mathematical Models ◽  
Temporal Dynamics ◽  
Bending Waves ◽  
Self Organized ◽  
Dynein Motor ◽  
Spatio Temporal ◽  
Cilia And Flagella ◽  
Nonlinear Nature ◽  
Selection Of

The physical basis of flagellar and ciliary beating is a major problem in biology which is still far from completely understood. The fundamental cytoskeleton structure of cilia and flagella is the axoneme, a cylindrical array of microtubule doublets connected by passive cross-linkers and dynein motor proteins. The complex interplay of these elements leads to the generation of self-organized bending waves. Although many mathematical models have been proposed to understand this process, few attempts have been made to assess the role of dyneins on the nonlinear nature of the axoneme. Here, we investigate the nonlinear dynamics of flagella by considering an axonemal sliding control mechanism for dynein activity. This approach unveils the nonlinear selection of the oscillation amplitudes, which are typically either missed or prescribed in mathematical models. The explicit set of nonlinear equations are derived and solved numerically. Our analysis reveals the spatio-temporal dynamics of dynein populations and flagellum shape for different regimes of motor activity, medium viscosity and flagellum elasticity. Unstable modes saturate via the coupling of dynein kinetics and flagellum shape without the need of invoking a nonlinear axonemal response. Hence, our work reveals a novel mechanism for the saturation of unstable modes in axonemal beating.

scholarly journals Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility

Science ◽  
2021 ◽  
Vol 371 (6525) ◽  
pp. eabd4914
Author(s):  
Sudarshan Gadadhar ◽  
Gonzalo Alvarez Viar ◽  
Jan Niklas Hansen ◽  
An Gong ◽  
Aleksandr Kostarev ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Male Fertility ◽  
Electron Tomography ◽  
Structural Basis ◽  
Cellular Functions ◽  
Flagellar Beat ◽  
Cryo Electron Tomography ◽  
Axonemal Dynein ◽  
Dynein Arms ◽  
Cilia And Flagella

Posttranslational modifications of the microtubule cytoskeleton have emerged as key regulators of cellular functions, and their perturbations have been linked to a growing number of human pathologies. Tubulin glycylation modifies microtubules specifically in cilia and flagella, but its functional and mechanistic roles remain unclear. In this study, we generated a mouse model entirely lacking tubulin glycylation. Male mice were subfertile owing to aberrant beat patterns of their sperm flagella, which impeded the straight swimming of sperm cells. Using cryo–electron tomography, we showed that lack of glycylation caused abnormal conformations of the dynein arms within sperm axonemes, providing the structural basis for the observed dysfunction. Our findings reveal the importance of microtubule glycylation for controlled flagellar beating, directional sperm swimming, and male fertility.

scholarly journals CO2 dynamics and heterogeneity in a cave atmosphere: role of ventilation patterns and airflow pathways

2021 ◽  
Author(s):  
Lovel Kukuljan ◽  
Franci Gabrovšek ◽  
Matthew D. Covington ◽  
Vanessa E. Johnston
Keyword(s):  
Temporal Variations ◽  
Observation Point ◽  
Spatially Distributed ◽  
Combined Action ◽  
Karst Systems ◽  
The Relationship ◽  
Co2 Dynamics ◽  
Global Carbon

AbstractUnderstanding the dynamics and distribution of CO2 in the subsurface atmosphere of carbonate karst massifs provides important insights into dissolution and precipitation processes, the role of karst systems in the global carbon cycle, and the use of speleothems for paleoclimate reconstructions. We discuss long-term microclimatic observations in a passage of Postojna Cave, Slovenia, focusing on high spatial and temporal variations of pCO2. We show (1) that the airflow through the massif is determined by the combined action of the chimney effect and external winds and (2) that the relationship between the direction of the airflow, the geometry of the airflow pathways, and the position of the observation point explains the observed variations of pCO2. Namely, in the terminal chamber of the passage, the pCO2 is low and uniform during updraft, when outside air flows to the site through a system of large open galleries. When the airflow reverses direction to downdraft, the chamber is fed by inlets with diverse flow rates and pCO2, which enter via small conduits and fractures embedded in a CO2-rich vadose zone. If the spatial distribution of inlets and outlets produces minimal mixing between low and high pCO2 inflows, high and persistent gradients in pCO2 are formed. Such is the case in the chamber, where vertical gradients of up to 1000 ppm/m are observed during downdraft. The results presented in this work provide new insights into the dynamics and composition of the subsurface atmosphere and demonstrate the importance of long-term and spatially distributed observations.

scholarly journals Functional interaction between dynein light chain and intermediate chain is required for mitotic spindle positioning

2011 ◽  
Vol 22 (15) ◽  
pp. 2690-2701 ◽  
Author(s):  
Melissa D. Stuchell-Brereton ◽  
Amanda Siglin ◽  
Jun Li ◽  
Jeffrey K. Moore ◽  
Shubbir Ahmed ◽  
...  
Keyword(s):  
Light Chain ◽  
Direct Evidence ◽  
Retrograde Transport ◽  
Cytoplasmic Dynein ◽  
Dynein Light Chain ◽  
Spindle Positioning ◽  
Dynein Motor ◽  
Intermediate Chains ◽  
Activator Complex

Cytoplasmic dynein is a large multisubunit complex involved in retrograde transport and the positioning of various organelles. Dynein light chain (LC) subunits are conserved across species; however, the molecular contribution of LCs to dynein function remains controversial. One model suggests that LCs act as cargo-binding scaffolds. Alternatively, LCs are proposed to stabilize the intermediate chains (ICs) of the dynein complex. To examine the role of LCs in dynein function, we used Saccharomyces cerevisiae, in which the sole function of dynein is to position the spindle during mitosis. We report that the LC8 homologue, Dyn2, localizes with the dynein complex at microtubule ends and interacts directly with the yeast IC, Pac11. We identify two Dyn2-binding sites in Pac11 that exert differential effects on Dyn2-binding and dynein function. Mutations disrupting Dyn2 elicit a partial loss-of-dynein phenotype and impair the recruitment of the dynein activator complex, dynactin. Together these results indicate that the dynein-based function of Dyn2 is via its interaction with the dynein IC and that this interaction is important for the interaction of dynein and dynactin. In addition, these data provide the first direct evidence that LC occupancy in the dynein motor complex is important for function.

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