Regulations of Microtubule Sliding by Ca²⁺ and cAMP and Their Roles in Forming Flagellar Waveforms

Abstract

ABSTRACT. The function of Ca2+ and cAMP in extruding doublet microtubules from sea urchin sperm axoneme and generating flagellar waves was investigated in order to clarify the regulatory mechanism of microtubule sliding and the formation mechanism of beating patterns of cilia and flagella. Almost all potentially asymmetric spermatozoa that were demembranated with Triton in the absence of Ca 2+ and reactivated with MgATP 2-(Gibbons, B.H. and Gibbons, I.R. (1980). J. Cell Biol., 84: 13-27), beat with planar waves closely resembling those of the intact spermatozoa, whereas potentially symmetric spermatozoa, in which axonemal calmodulin was removed by detergent extraction in the presence of millimolar Ca 2+ (Brokaw, C.J. and Nagayama, S.M. (1985). J. Cell Biol., 100: 1875-1883), beat with three-dimensional waves if they were reactivated with low MgATP 2-. At a high MgATP 2-, almost all demembranated spermatozoa beat with planar waves. cAMP enhanced the threedimensionality of the flagellar waves at a low Ca 2+ . These changes in the flagellar waves were caused by different regulations of the microtubule sliding by calcium, cAMP, and MgATP 2-.

Functional anatomy of the mammalian sperm flagellum

“…It has been established that elevated Ca 21 has a stimulatory action on sliding of doublets 1-4 (Lesich et al, 2012) and possibly also an inhibitory action on force generated by the opposing set of doublets, 7-9 (Lesich et al, 2014). We suspect this may underlie the action of Ca 21 on motility, as evidence also supports a change in the activity pattern of the dynein on the two sides of the axoneme during hyperactivation (Ishijima, 2013(Ishijima, , 2015. In the simple flagella of Chlamydomonas there is evidence for Ca 21 regulatory elements interacting with specific dyneins (King and Patel-King, 1995;LeDizet and Piperno, 1995;Wirschell et al, 2007) and it is likely that similar regulatory pathways are also present in mammalian sperm flagella.…”

“…There is strong evidence that Ca 21 has a disproportionate effect on the dynein motors located on one side of the ring of doublets (Lesich et al, 2012(Lesich et al, , 2014Ishijima, 2013Ishijima, , 2015Lindemann et al, 1992). There is also some basis to suspect that elevated Ca 21 may lock certain dyneins into a sustained state of activation, such that the production of force and bending torque acting to bend the flagellum in one direction has a sustained component which does not "switch" with the period of the beat cycle (Brokaw, 1979;Eshel and Brokaw, 1987;Lesich et al, 2014).…”

Ca²⁺ and cAMP regulations of microtubule sliding in hyperactivated motility of bull spermatozoa

“…23 , 24 ) Furthermore, a recent investigation on the relationship between the microtubule sliding and flagellar movement of sea urchin spermatozoa revealed that various types of flagellar movement, including planar and helical movement, were induced by Ca 2+ , cAMP, and MgATP 2− regulation of microtubule sliding. 25 ) Taking into account these results, hypothetical diagrams of flagellar disintegration by microtubule sliding are drawn (Fig. 10 ).…”

cAMP controls the balance of the propulsive forces generated by the two flagella of Chlamydomonas

“…The bending movement is controlled by membrane potential and second messengers such as Ca 21 , cAMP, and cGMP. Examples include increased ciliary motility in airway epithelial cells and sperm [Lindemann, 1978;Tamaoki et al, 1985;Schmid et al, 2006], initiation of trout and tunicate sperm motility [Morisawa and Okuno, 1982;Nomura et al, 2000;Shiba and Inaba, 2014], and increased three-dimensional components in sea urchin sperm [Ishijima, 2013]. The reversal and augmentation of ciliary beats are brought about by an increase in intracellular Ca 21 and cAMP concentrations, respectively [Naito and Kaneko, 1972;Bonini and Nelson, 1988].…”

“…Motility of cilia and flagella of many other cells and organisms are also controlled by cAMP [Tash and Means, 1983]. Examples include increased ciliary motility in airway epithelial cells and sperm [Lindemann, 1978;Tamaoki et al, 1985;Schmid et al, 2006], initiation of trout and tunicate sperm motility [Morisawa and Okuno, 1982;Nomura et al, 2000;Shiba and Inaba, 2014], and increased three-dimensional components in sea urchin sperm [Ishijima, 2013]. Moreover, cAMP is involved in signal transduction in sensory olfactory cilia [Pace et al, 1985;Kurahashi, 1990] and ciliogenesis [Besschetnova et al, 2010].…”