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

Abstract

To reach and fertilize the egg, mammalian spermatozoa change their flagellar movement in the female reproductive tract, named hyperactivation. The biochemical analyses of the hyperactivated movement using demembranated spermatozoa defined the factors inducing this peculiar movement; namely, large asymmetrical flagellar movement observed in the early stage of the hyperactivation was induced with a high Ca2+ concentration while large symmetrical flagellar movement in the late stage of the hyperactivation was generated with low Ca2+ and high cAMP concentrations. Under these conditions, the microtubule sliding of bull sperm flagella was investigated by disintegrating the sperm flagella with MgATP2− after extracting their plasma membrane and mitochondria. The large asymmetrical flagellar movement was caused by a long sliding displacement of a fiber of the doublet microtubules. On the other hand, the large symmetrical flagellar movement was generated by a large amount of microtubule sliding by many doublet microtubules.

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.…”

“…By a mechanism still only partially elucidated, Ca 21 most likely changes the activity of a subset of dynein arms on specific doublets, and hence, changes the parameters of the beat cycle (Lesich et al, 2012;Ishijima, 2015). Since Ca 21 is known to be a critical trigger in hyperactivation, it may be that select subpopulations of dynein are drawn into action to trigger the transition.…”

“…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).…”

Self-Sustained Oscillatory Sliding Movement of Doublet Microtubules and Flagellar Bend Formation

“…The author recently revealed that there are two types of microtubule sliding events regulated by Ca 2+ and cAMP: (i) large sliding displacement generated by sliding synchronously throughout an extended region along one doublet and (ii) small sliding displacement generated by sliding that propagated circumferentially around the axoneme from one doublet to another along the axoneme. The first presumably corresponds to the synchronous sliding and the second the metachronal sliding [ 1 , 2 ]. The different ways of regulating microtubule sliding using Ca 2+ , cAMP, and MgATP 2- lead to various types of flagellar movements, including planar or helical bending in sea urchin spermatozoa [ 1 ].…”

“…The different ways of regulating microtubule sliding using Ca 2+ , cAMP, and MgATP 2- lead to various types of flagellar movements, including planar or helical bending in sea urchin spermatozoa [ 1 ]. Furthermore, these regulations generate a hyperactivated motility of mammalian spermatozoa [ 2 ].…”