Sperm-specific protein kinase A catalytic subunit Cα ₂ orchestrates cAMP signaling for male fertility

• Michael A. Nolan

  Departments of Pharmacology and Physiology and Biophysics, University of Washington, Seattle, WA 98195; and Department of Anatomy and Cell Biology, Philipps University, D35037 Marburg, Germany

• Donner F. Babcock

  Departments of Pharmacology and Physiology and Biophysics, University of Washington, Seattle, WA 98195; and Department of Anatomy and Cell Biology, Philipps University, D35037 Marburg, Germany

• Gunther Wennemuth

  Departments of Pharmacology and Physiology and Biophysics, University of Washington, Seattle, WA 98195; and Department of Anatomy and Cell Biology, Philipps University, D35037 Marburg, Germany

• William Brown

  Departments of Pharmacology and Physiology and Biophysics, University of Washington, Seattle, WA 98195; and Department of Anatomy and Cell Biology, Philipps University, D35037 Marburg, Germany

• Kimberly A. Burton

  Departments of Pharmacology and Physiology and Biophysics, University of Washington, Seattle, WA 98195; and Department of Anatomy and Cell Biology, Philipps University, D35037 Marburg, Germany

• G. Stanley McKnight

  Departments of Pharmacology and Physiology and Biophysics, University of Washington, Seattle, WA 98195; and Department of Anatomy and Cell Biology, Philipps University, D35037 Marburg, Germany

抄録

An unusual cAMP signaling system mediates many of the events that prepare spermatozoa to meet the egg. Its components include the atypical, bicarbonate-stimulated, sperm adenylyl cyclase and a cAMP-dependent protein kinase (PKA) with the unique catalytic subunit termed Cα 2 or C s . We generated mice that lack Cα 2 to determine its importance in the events downstream of cAMP production. Male Cα 2 null mice produce normal numbers of sperm that swim spontaneously in vitro . Thus, Cα 2 has no required role in formation of a functional flagellum or the initiation of motility. In contrast, we find that Cα 2 is required for bicarbonate to speed the flagellar beat and facilitate Ca 2+ entry channels. In addition, Cα 2 is needed for the protein tyrosine phosphorylation that occurs late in the sequence of sperm maturation and for a negative feedback control of cAMP production, revealed here. Consistent with these specific defects in several important sperm functions, Cα 2 null males are infertile despite normal mating behavior. These results define several crucial roles of PKA in sperm cell biology, bringing together both known and unique PKA-mediated events that are necessary for male fertility.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 101 (37), 13483-13488, 2004-08-31

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1363388844167774848
• NII論文ID: 80016895951
• DOI: 10.1073/pnas.0405580101
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.0405580101
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