Cyclic GMP-specific phosphodiesterase-5 regulates motility of sea urchin spermatozoa.
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 approximately 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.
Su
Yi-Hsien
YH
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093-0202, USA.
Vacquier
Victor D
VD
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D017124:Conserved Sequence; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010802:Phylogeny; D012617:Sea Urchins / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology*; D016415:Sequence Alignment; D013081:Sperm Motility / Q000502:physiology*; D013094:Spermatozoa / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology*
D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D006152:Cyclic GMP