title: The development of signal transduction pathways during epididymal maturation is calcium dependent.
abstract: Capacitation has been correlated with the activation of a cAMP-PKA-dependent signaling pathway leading to protein tyrosine phosphorylation. The ability to exhibit this response to cAMP matures during epididymal maturation in concert with the ability of the spermatozoa to capacitate. In this study, we have addressed the mechanisms by which spermatozoa gain the potential to activate this signaling pathway during epididymal maturation. In a modified Tyrode's medium containing 1.7 mM calcium, caput spermatozoa had significantly higher [Ca2+]i than caudal cells and could not tyrosine phosphorylate in response to cAMP. However, in calcium-depleted medium both caput and caudal cells could exhibit a cAMP-dependent phosphorylation response. The inhibitory effect of calcium on tyrosine phosphorylation was also observed in caudal spermatozoa using thapsigargin, a Ca(2+)-ATPase inhibitor that increased [Ca2+]i and precipitated a corresponding decrease in phosphotyrosine expression. We also demonstrate that despite the activation of tyrosine phosphorylation in caput spermatozoa, these cells remain nonfunctional in terms of motility, sperm-egg recognition and acrosomal exocytosis. These results demonstrate that the signaling pathway leading to tyrosine phosphorylation in mouse spermatozoa is negatively regulated by [Ca2+]i, and that maturation mechanisms that control [Ca2+]i within the spermatozoon are critically important during epididymal transit.
authors.affiliation: Discipline of Biological Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Heath
authors.initials: H
authors.lastname: Ecroyd
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Asquith
authors.forename: Russell C
authors.initials: RC
authors.lastname: Jones
authors.forename: R John
authors.initials: RJ
authors.lastname: Aitken
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004822:Epididymis / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction; D013084:Sperm-Ovum Interactions; D013094:Spermatozoa / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D014443:Tyrosine; D019284:Thapsigargin; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium