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J Biol Chem, Vol. 274, Issue 34, 24131-24136, August 20, 1999
From the Departments of Cyclic AMP stimulates sperm motility in a variety
of mammalian species, but the molecular details of the intracellular
signaling pathway responsible for this effect are unclear. The type
II
Deletion of Type II
Regulatory Subunit Delocalizes Protein
Kinase A in Mouse Sperm without Affecting Motility or
Fertilization
,,, and
Pharmacology and
§ Urology, University of Washington School of Medicine,
Seattle, Washington 98195-7750
isoform of protein kinase A (PKA) is induced late in
spermatogenesis and is thought to localize PKA to the flagellar
apparatus where it binds cAMP and stimulates motility. A targeted
disruption of the type II regulatory subunit (RII) gene allowed
us to examine the role of PKA localization in sperm motility and
fertility. In wild type sperm, PKA is found primarily in the
detergent-resistant particulate fraction and localizes to the
mitochondrial-containing midpiece and the principal piece. In mutant
sperm, there is a compensatory increase in RI protein and a dramatic
relocalization of PKA such that the majority of the holoenzyme now
appears in the soluble fraction and colocalizes with the cytoplasmic
droplet. Unexpectedly the RII mutant mice are fertile and have no
significant changes in sperm motility. Our results demonstrate that the
highly localized pattern of PKA seen in mature sperm is not essential for motility or fertilization.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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