The "soluble" adenylyl cyclase in sperm mediates multiple signaling events required for fertilization.
Mammalian fertilization is dependent upon a series of bicarbonate-induced, cAMP-dependent processes sperm undergo as they "capacitate," i.e., acquire the ability to fertilize eggs. Male mice lacking the bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC), the predominant source of cAMP in male germ cells, are infertile, as the sperm are immotile. Membrane-permeable cAMP analogs are reported to rescue the motility defect, but we now show that these "rescued" null sperm were not hyperactive, displayed flagellar angulation, and remained unable to fertilize eggs in vitro. These deficits uncover a requirement for sAC during spermatogenesis and/or epididymal maturation and reveal limitations inherent in studying sAC function using knockout mice. To circumvent this restriction, we identified a specific sAC inhibitor that allowed temporal control over sAC activity. This inhibitor revealed that capacitation is defined by separable events: induction of protein tyrosine phosphorylation and motility are sAC dependent while acrosomal exocytosis is not dependent on sAC.
Hess
Kenneth C
KC
Department of Pharmacology, Joan and Sanford Weill Medical College, Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA.
Jones
Brian H
BH
Marquez
Becky
B
Chen
Yanqiu
Y
Ord
Teri S
TS
Kamenetsky
Margarita
M
Miyamoto
Catarina
C
Zippin
Jonathan H
JH
Kopf
Gregory S
GS
Suarez
Susan S
SS
Levin
Lonny R
LR
Williams
Carmen J
CJ
Buck
Jochen
J
Moss
Stuart B
SB
D000177:Acrosome / Q000502:physiology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D005089:Exocytosis; D005306:Fertilization / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012995:Solubility; D013075:Sperm Capacitation / Q000187:drug effects; D013081:Sperm Motility; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D014443:Tyrosine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases