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Vol. 17, Issue 1, 114-121, January 2006

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Cyclic GMP-specific Phosphodiesterase-5 Regulates Motility of Sea Urchin Spermatozoa

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093-0202

Submitted August 31, 2005; Revised October 7, 2005; Accepted October 11, 2005
Monitoring Editor: Marianne Bronner-Fraser

Motility, chemotaxis, and the acrosome reaction of animal sperm are all regulated by cyclic nucleotides and protein phosphorylation. One of the cyclic AMP-dependent protein kinase (PKA) substrates in sea urchin sperm is a member of the phosphodiesterase (PDE) family. The molecular identity and in vivo function of this PDE remained unknown. Here we cloned and characterized this sea urchin sperm PDE (suPDE5), which is an ortholog of human PDE5. The recombinant catalytic domain of suPDE5 hydrolyzes only cyclic GMP (cGMP) and the activity is pH-dependent. Phospho-suPDE5 localizes mainly to sperm flagella and the phosphorylation increases when sperm contact the jelly layer surrounding eggs. In vitro dephosphorylation of suPDE5 decreases its activity by 50%. PDE5 inhibitors such as Viagra block the activity of suPDE5 and increase sperm motility. This is the first PDE5 protein to be discovered in animal sperm. The data are consistent with the hypothesis that suPDE5 regulates cGMP levels in sperm, which in turn modulate sperm motility.

Abbreviations used: ASW, artificial seawater; cGMP, cyclic guanine monophosphate; EJ, egg jelly; GAF, a conserved domain found in cGMP-binding and stimulated PDEs, Anabaena adenylyl cyclases, and Escherichia coli FhlA protein; PDE, phosphodiesterase; PKA, cAMP-dependent protein kinase; pHi, intracellular pH.

Address correspondence to: V. D. Vacquier (vvacquier{at}ucsd.edu).