The 'Soluble' Adenylyl Cyclase in Sperm Mediates Multiple Signaling Events Required for Fertilization
| Autor: | Kenneth C. Hess, Susan S. Suarez, Becky Marquez, Catarina Miyamoto, Gregory S. Kopf, Stuart B. Moss, Jochen Buck, Brian H. Jones, Teri Ord, Jonathan H. Zippin, Lonny R. Levin, Margarita Kamenetsky, Yanqiu Chen, Carmen J. Williams |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Motility Biology General Biochemistry Genetics and Molecular Biology Adenylyl Cyclase Inhibitors Article Exocytosis 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Capacitation Internal medicine medicine Cyclic AMP Animals Phosphorylation education Molecular Biology Sperm motility 030304 developmental biology Mice Knockout 0303 health sciences education.field_of_study 030219 obstetrics & reproductive medicine Tyrosine phosphorylation Cell Biology Soluble adenylyl cyclase Sperm Spermatozoa Cell biology Endocrinology chemistry Solubility Fertilization embryonic structures Sperm Motility Tyrosine Spermatogenesis Acrosome Sperm Capacitation Adenylyl Cyclases Signal Transduction Developmental Biology |
| Zdroj: | Developmental Cell. 9(2):249-259 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2005.06.007 |
| Popis: | SummaryMammalian 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. |
| Databáze: | OpenAIRE |
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