Cyclic Adenosine 3′,5′ Monophosphate, Calcium and Protein Phosphorylation in Flagellar Motility

Abstract

cAMP and calcium are two important regulators of sperm flagellar motility. cAMP stimulates sperm motility by activating cAMP-dependent protein kinase and catalyzing the phosphorylation of sperm proteins. The stimulation of sperm motility by cAMP appears to be at two different levels. Evidence has been presented to suggest that cAMP-dependent phosphorylations may be required in order for motility to be initiated. In addition, cAMP-dependent phosphorylation appears to modulate specific parameters of motility resulting in higher beat frequency or greater wave amplitude. Calcium, on the other hand, when elevated intracellularly to 10(-6) M or higher, inhibits flagellar motility. The calcium-binding protein, calmodulin, appears to mediate a large number of effects of calcium on motility. Evidence suggests that calcium-calmodulin may be involved at the level of the membrane to pump calcium out of the flagellum. In addition, calcium-calmodulin may be involved in the control of axonemal function by regulating dynein ATPase and myosin light chain kinase activities. The identification of cAMP-dependent protein kinase, calmodulin and myosin light chain kinase in the sperm head suggests that cAMP and calcium-dependent phosphorylations are also involved in the control of the fertilization process, i.e., the acrosome reaction, in a manner similar to that known for the control of stimulus/secretion coupling. Finally, the effects of cAMP on flagellar motility are mediated by protein phosphorylation while the effects of calcium on motility are also in part, mediated by effects on protein phosphorylation.

Supplementation of biotin to sperm preparation medium increases the motility and longevity in cryopreserved human spermatozoa

“…However, our observations confirm that pentoxifylline can significantly enhance the motility of spermatozoa subjected to freezethaw process, both in normozoospermic and abnormal semen samples. The enhanced motility induced by pentoxifylline is due to its inhibitory effect on phosphodiesterase, which in turn helps in maintaining a high intracellular cyclic adenosine monophosphate (cAMP) level in the spermatozoa [18]. A marginal decline in motility with the increase in the incubation time observed in pentoxifylline group may be due to the failure of maintaining an elevated level of cAMP in the cytoplasm of the frozen-thawed spermatozoa.…”

The radial spokes and central apparatus: Mechano‐chemical transducers that regulate flagellar motility

“…Motility changes mediated by these second messengers include inducing quiescence in beating flagella, activating motility, increasing beat frequency, reversing the direction of the effective stroke, or changing waveform. The effect of second messengers is mediated at least in part through second-messenger-dependent kinases and phosphatases, such as cAMP-dependent protein kinase A (PKA), cGMP-dependent protein kinase (PKG), calmodulin dependent kinase, and calcineurin (PP2B) [Tash and Means, 1983;Tash et al, 1988;Chaudhry et al, 1995;San Agustin et al, 1998;Smith, 2002a]. It is possible that some second messengers affect motility by additional mechanisms that are independent of phosphorylation.…”

Enzymes of adenosine metabolism in mouse sperm suspensions

“…A well-defined system for capacitation of epididymal mouse spermatozoa and fertilization of homologous eggs in vitro has allowed investi¬ gation of a number of compounds which influence these processes (Fraser, 1983). Cyclic AMP (cAMP) appears to play a key role in modulating many capacitation-related events (Tash & Means, 1983); observation of increased adenylate cyclase and decreased phosphodiesterase activities during capacitation of mouse spermatozoa in vitro support this view (Stein & Fraser, 1984;Monks et ai, 1986;Monks & Fraser, 1987). However, the control of sperm cAMP production remains obscure since, unlike the enzyme of somatic cells, sperm adenylate cyclase is not hormonecontrolled (Hildebrandt et ai, 1985).…”