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AKAP3 Selectively Binds PDE4A Isoforms in Bovine Spermatozoa¹

Department of Medicine,³ Oregon Health and Sciences University and VA Medical Center, Portland, Oregon 97239 Department of Biological Sciences,⁴ Kent State University, Kent, Ohio 44242 Department of Cell Biology,⁵ Vanderbilt University, Nashville, Tennessee 37232-2175 Department of Obstetrics and Gynecology,⁶ Stanford University, Stanford, California 94305-5317

ABSTRACT

Cyclic AMP plays an important role in regulating sperm motility and acrosome reaction through activation of cAMP-dependent protein kinase A (PKA). Phosphodiesterases (PDEs) modulate the levels of cyclic nucleotides by catalyzing their degradation. Although PDE inhibitors specific to PDE1 and PDE4 are known to alter sperm motility and capacitation in humans, little is known about the role or subcellular distribution of PDEs in spermatozoa. The localization of PKA is regulated by A-kinase anchoring proteins (AKAPs), which may also control the intracellular distribution of PDE. The present study was undertaken to investigate the role and localization of PDE4 during sperm capacitation. Addition of Rolipram or RS25344, PDE4-specific inhibitors significantly increased the progressive motility of bovine spermatozoa. Immunolocalization techniques detected both PDE4A and AKAP3 (formerly known as AKAP110) in the principal piece of bovine spermatozoa. The PDE4A5 isoform was detected primarily in the Triton X-100-soluble fraction of caudal epididymal spermatozoa. However, in ejaculated spermatozoa it was seen primarily in the SDS-soluble fraction, indicating a shift in PDE4A5 localization into insoluble organelles during sperm capacitation. AKAP3 was detected only in the SDS-soluble fraction of both caudal and ejaculated sperm. Immunoprecipitation experiments using COS cells cotransfected with AKAP3 and either Pde4a5 or Pde4d provide evidence that PDE4A5 but not PDE4D interacts with AKAP3. Pulldown assays using sperm cell lysates confirm this interaction in vitro. These data suggest that AKAP3 binds both PKA and PDE4A and functions as a scaffolding protein in spermatozoa to regulate local cAMP concentrations and modulate sperm functions.

phosphodiesterases, signal transduction, sperm, sperm motility, transport

¹ Supported by NIH Grants HD36408 (D.W.C.) and VA Merit Award (D.W.C.), NIH Grant HD38520 (S.V.), and HD31544 (M.C.).

² Correspondance: Daniel W. Carr, Veterans Affairs Medical Center, Mail Code R&D8, 3710 SW US Veterans Hospital Road, Portland, OR 97239. FAX: 503 721 1082; carrd{at}ohsu.edu

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				S. E Fiedler, M. Bajpai, and D. W Carr Identification and Characterization of RHOA-Interacting Proteins in Bovine Spermatozoa Biol Reprod, January 1, 2008; 78(1): 184 - 192. [Abstract] [Full Text] [PDF]