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PMID: 16177223 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

AKAP3 selectively binds PDE4A isoforms in bovine spermatozoa.

Biology of reproduction ·Vol. 74 ·No. 1 ·2006-01-00 ·Pages 109-18

Bajpai M, Fiedler SE, Huang Z, Vijayaraghavan S, Olson GE, Livera G, Conti M, Carr DW

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.

MeSH Terms
3',5'-Cyclic-AMP Phosphodiesterases/metabolism Adaptor Proteins, Signal Transducing/metabolism Animals Cattle Cyclic AMP-Dependent Protein Kinases Cyclic Nucleotide Phosphodiesterases, Type 1 Cyclic Nucleotide Phosphodiesterases, Type 4 Fluorescent Antibody Technique Immunoprecipitation Isoenzymes Male Phosphorylation Solubility Sperm Maturation/physiology Sperm Motility/physiology Spermatozoa/metabolism,physiology
Chemicals
Adaptor Proteins, Signal Transducing Isoenzymes Cyclic AMP-Dependent Protein Kinases 3',5'-Cyclic-AMP Phosphodiesterases Cyclic Nucleotide Phosphodiesterases, Type 1 Cyclic Nucleotide Phosphodiesterases, Type 4
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bajpai Malini
Department of Medicine, Oregon Health and Sciences University and VA Medical Center, Portland, OR 97239, USA.
Fiedler Sarah E
Huang Zaohua
Vijayaraghavan Srinivasan
Olson Gary E
Livera Gabriel
Conti Marco
Carr Daniel W
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Article Info
Journal
Biology of reproduction
Abbr.
Biol Reprod
ISSN
0006-3363
DOI
10.1095/biolreprod.105.043588
Published
2006-01-00
Epub
2005-00-21
Pages
109-18
Language
English
Region
United States
NLM ID
0207224
PMCID
PMC1352331
Subset
IM
Grants
NICHD NIH HHS · R01 HD036408 · United States
NICHD NIH HHS · HD31544 · United States
NICHD NIH HHS · HD38520 · United States
NICHD NIH HHS · R01 HD038520 · United States
NICHD NIH HHS · HD36408 · United States
NICHD NIH HHS · R01 HD031544 · United States
External Links
PubMed source DOI: 10.1095/biolreprod.105.043588 PMC Full Text View journal details
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