title: Soluble adenylyl cyclase is required for activation of sperm but does not have a direct effect on hyperactivation.
abstract: Soluble adenylyl cyclase (SACY) is an essential component of cAMP-signalling cascades that activate sperm motility and capacitate sperm. SACY activity is stimulated by HCO(3)(-) and Ca(2+). Sperm from Sacy(-/-) (null) mice were immotile or weakly motile, but cAMP analogues N(6),2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) and adenosine 3',5'-cyclic monophosphate acetoxymethyl ester (cAMP-AM) activated motility. Null sperm activated by dbcAMP quickly developed hairpin bends at the junction of the midpiece and principal piece, which could be prevented by omitting HCO(3)(-). Treating Sacy(-/-) sperm with thimerosal or NH(4)Cl to raise flagellar cytoplasmic Ca(2+) could not substitute for cAMP analogues in activating motility; however, sperm activated with cAMP-AM hyperactivated after thimerosal treatment. Treating activated wild-type sperm with SACY inhibitor KH7 did not prevent hyperactivation from developing during capacitation in vitro, although high doses impaired motility. These results indicate that, while the SACY/cAMP signalling pathway is required for motility activation, it is not directly involved in triggering hyperactivation.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Becky
authors.initials: B
authors.lastname: Marquez
authors.forename: Susan S
authors.initials: SS
authors.lastname: Suarez
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000643:Ammonium Chloride; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology*; D013075:Sperm Capacitation / Q000502:physiology*; D013081:Sperm Motility / Q000502:physiology*; D013849:Thimerosal
chemical_list: D000643:Ammonium Chloride; D013849:Thimerosal; D003994:Bucladesine; D000262:Adenylyl Cyclases