Calcium ions tune the beats of cilia and flagella

The cytoskeleton of cilia and flagella is so called axoneme a stable cylindrical architecture of nine microtubule doublets. Axoneme performs periodic bending motion by utilizing specific dynein motor family powered by ATP hydrolysis. It is still unclear how this highly organized "ciliary beat" is being initiated and strongly coordinated by the combined action of hundreds dynein motors. Based on the experimental evidences we here elaborate a plausible scenario in which actually calcium ions play the roles of catalytic activators and coordinators of dynein attachments doing it in superposition with already known mechanical control tools of "ciliary beat". Polyelectrolyte properties of microtubules incorporated in axoneme doublets enable the formation and propagation of soliton-like "ionic clouds" of Ca2+ ions along these "coaxial nanocables". The sliding speed of such Ca2+ "clouds" along microtubule doublets is comparable with the speed of propagation of "ciliary beat" itself. We elaborated the interplay between influx of Ca2+ ions in ciliary based body and the sliding of microtubule triplets therein. In second segment we considered how the dynein motors activated by Ca2+ ions contained within solitonic "ionic clouds" in competition with axoneme curvature regulate ciliary and flagellar beating.

[1]  D. Clapham,et al.  Primary cilia are specialized calcium signaling organelles , 2013, Nature.

[2]  Jack A. Tuszynski,et al.  Nonlinear calcium ion waves along actin filaments control active hair–bundle motility , 2018, bioRxiv.

[3]  Hitoshi Sakakibara,et al.  Chlamydomonas outer arm dynein alters conformation in response to Ca2+. , 2007, Molecular biology of the cell.

[4]  Elizabeth F. Smith Regulation of flagellar dynein by calcium and a role for an axonemal calmodulin and calmodulin-dependent kinase. , 2002, Molecular biology of the cell.

[5]  C. Brokaw,et al.  Thinking about flagellar oscillation. , 2009, Cell motility and the cytoskeleton.

[6]  H. Cantiello,et al.  Electrical Oscillations in Two-Dimensional Microtubular Structures , 2016, Scientific Reports.

[7]  V. Redeker Mass spectrometry analysis of C-terminal posttranslational modifications of tubulins. , 2010, Methods in cell biology.

[8]  Yoshiaki Iwadate,et al.  Photolysis of caged calcium in cilia induces ciliary reversal in Paramecium caudatum , 2003, Journal of Experimental Biology.

[9]  N. Ralević,et al.  A nonlinear model of ionic wave propagation along microtubules , 2009, European Biophysics Journal.

[10]  Veikko F. Geyer,et al.  Motor regulation results in distal forces that bend partially disintegrated Chlamydomonas axonemes into circular arcs. , 2014, Biophysical journal.

[11]  P. Sartori Effect of curvature and normal forces on motor regulation of cilia , 2019, 1905.04138.

[12]  Ingmar H. Riedel-Kruse,et al.  How molecular motors shape the flagellar beat , 2007, HFSP journal.

[13]  H. Plattner,et al.  Sub-second cellular dynamics: time-resolved electron microscopy and functional correlation. , 2006, International review of cytology.

[14]  S. King Turning dyneins off bends cilia , 2018, Cytoskeleton.

[15]  R. Kamiya,et al.  Functional Diversity of Axonemal Dyneins as Assessed by in Vitro and in Vivo Motility Assays of Chlamydomonas Mutants , 2014, Zoological Science.

[16]  H. Yost,et al.  The roles of cilia in developmental disorders and disease , 2006, Development.

[17]  P. P. Yupapin,et al.  Solitonic conduction of electrotonic signals in neuronal branchlets with polarized microstructure , 2017, Scientific Reports.

[18]  Wanlin Guo,et al.  Ion Permeability of a Microtubule in Neuron Environment. , 2018, The journal of physical chemistry letters.

[19]  S. King,et al.  Calcium Regulates ATP-sensitive Microtubule Binding by Chlamydomonas Outer Arm Dynein* , 2003, Journal of Biological Chemistry.

[20]  C. Brokaw Computer simulation of flagellar movement VIII: coordination of dynein by local curvature control can generate helical bending waves. , 2002, Cell motility and the cytoskeleton.

[21]  G. S. Manning Approximate Solutions to Some Problems in Polyelectrolyte Theory Involving Nonuniform Charge Distributions , 2008 .

[22]  Ying Zhu,et al.  The Catsper channel and its roles in male fertility: a systematic review , 2017, Reproductive Biology and Endocrinology.

[23]  K. Gull,et al.  Direction of flagellum beat propagation is controlled by proximal/distal outer dynein arm asymmetry , 2018, Proceedings of the National Academy of Sciences.

[24]  E. Muto,et al.  Dielectric measurement of individual microtubules using the electroorientation method. , 2006, Biophysical journal.

[25]  Jonathon Howard,et al.  Mechanical signaling in networks of motor and cytoskeletal proteins. , 2009, Annual review of biophysics.

[26]  T. Abe,et al.  Asymmetric distribution of dynamic calcium signals in the node of mouse embryo during left-right axis formation. , 2013, Developmental biology.

[27]  C. Lindemann The Geometric Clutch as a Working Hypothesis for Future Research on Cilia and Flagella , 2007, Annals of the New York Academy of Sciences.

[28]  N. Klauke,et al.  One-way calcium spill-over during signal transduction in Paramecium cells: from the cell cortex into cilia, but not in the reverse direction. , 2004, Cell calcium.

[29]  Sudipto Roy,et al.  Left–right asymmetry: cilia stir up new surprises in the node , 2013, Open Biology.

[30]  J. McIntosh,et al.  The Molecular Architecture of Axonemes Revealed by Cryoelectron Tomography , 2006, Science.

[31]  Jack A. Tuszynski,et al.  How signals of calcium ions initiate the beats of cilia and flagella , 2019, Biosyst..

[32]  D. Woolley,et al.  Basal sliding and the mechanics of oscillation in a mammalian sperm flagellum. , 2004, Biophysical journal.

[33]  H. Cantiello,et al.  Effect of Calcium on Electrical Energy Transfer by Microtubules , 2008, Journal of biological physics.

[34]  F. Jülicher,et al.  Auditory sensitivity provided by self-tuned critical oscillations of hair cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[35]  W. Sale,et al.  Fifty years of microtubule sliding in cilia , 2018, Molecular biology of the cell.

[36]  D. Clapham,et al.  Direct recording and molecular identification of the calcium channel of primary cilia , 2013, Nature.

[37]  H. Cantiello,et al.  Two-Dimensional Brain Microtubule Structures Behave as Memristive Devices , 2019, Scientific Reports.

[38]  D. Clapham,et al.  Ion channels and calcium signaling in motile cilia , 2015, eLife.

[39]  M. Berridge,et al.  Calcium signalling: dynamics, homeostasis and remodelling , 2003, Nature reviews. Molecular cell biology.

[40]  D. Sekulic,et al.  Nonlinear dynamics of C-terminal tails in cellular microtubules. , 2016, Chaos.

[41]  Mitsutoshi Setou,et al.  Tubulin polyglutamylation is essential for airway ciliary function through the regulation of beating asymmetry , 2010, Proceedings of the National Academy of Sciences.

[42]  Zuzanna S Siwy,et al.  Calcium-induced voltage gating in single conical nanopores. , 2006, Nano letters.

[43]  P. Satir,et al.  Overview of structure and function of mammalian cilia. , 2007, Annual review of physiology.

[44]  J. Tuszynski,et al.  Nonlinear ionic pulses along microtubules , 2011, The European physical journal. E, Soft matter.

[45]  B. Frieden,et al.  Cellular information dynamics through transmembrane flow of ions , 2017, Scientific Reports.

[46]  M. Marucho,et al.  A multi-scale approach to describe electrical impulses propagating along actin filaments in both intracellular and in vitro conditions , 2018, RSC advances.

[47]  M. Matsen Compression of polyelectrolyte brushes in a salt-free theta solvent , 2011, The European physical journal. E, Soft matter.

[48]  Kate S. Wilson,et al.  Equations of interdoublet separation during flagella motion reveal mechanisms of wave propagation and instability. , 2014, Biophysical journal.

[49]  Emil Alexov,et al.  Cytoplasmic dynein binding, run length, and velocity are guided by long-range electrostatic interactions , 2016, Scientific Reports.

[50]  M. Zivanov,et al.  Solitonic Ionic Currents Along Microtubules , 2010 .

[51]  J. Tuszynski,et al.  Investigation of the Electrical Properties of Microtubule Ensembles under Cell-Like Conditions , 2019, Nanomaterials.

[52]  G. I. Bell Models for the specific adhesion of cells to cells. , 1978, Science.

[53]  Avner Priel,et al.  A biopolymer transistor: electrical amplification by microtubules. , 2006, Biophysical journal.

[54]  T. Furuta,et al.  Real-time analysis of the role of Ca2+ in flagellar movement and motility in single sea urchin sperm , 2005, The Journal of cell biology.

[55]  R. Burgoyne,et al.  Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signalling , 2007, Nature Reviews Neuroscience.

[56]  G. S. Manning A counterion condensation theory for the relaxation, rise, and frequency dependence of the parallel polarization of rodlike polyelectrolytes , 2011, The European physical journal. E, Soft matter.

[57]  H. Cantiello,et al.  Bundles of Brain Microtubules Generate Electrical Oscillations , 2018, Scientific Reports.

[58]  C Shingyoji,et al.  Calcium regulation of microtubule sliding in reactivated sea urchin sperm flagella. , 2000, Journal of cell science.

[59]  C. Dey,et al.  Reactivation of flagellar motility in demembranated Leishmania reveals role of cAMP in flagellar wave reversal to ciliary waveform , 2016, Scientific Reports.

[60]  Veikko F. Geyer,et al.  Dynamic curvature regulation accounts for the symmetric and asymmetric beats of Chlamydomonas flagella , 2015, eLife.