rab 3-peptide stimulates exocytosis of the ram sperm acrosome via interaction with cyclic AMP and phospholipase A2 metabolites.
Acrosomal exocytosis triggered with A23187/Ca2+ was enhanced by rab3AL, a synthetic peptide corresponding to the effector domain of the small GTP-binding protein rab3. Exocytosis was further enhanced when spermatozoa were also exposed to dibutyryl-cAMP, but was prevented when H-89, a protein kinase A (PKA) inhibitor, was included. The action of rab3AL was not on, or upstream of, phospholipase A2 (PLA2). Inhibition of exocytosis by the PLA2 inhibitor aristolochic acid was overcome by rab3AL when it was included together with lysophosphatidylcholine; this effect was prevented by H-89. These results suggest a functional coupling between rab3 protein, metabolites generated by PLA2, and cAMP-activated PKA, in the final steps leading to membrane fusion during acrosomal exocytosis.
Garde
J
J
Department of Development and Signalling, Babraham Institute, Cambridge, UK.
Roldan
E R
ER
D000177:Acrosome / Q000187:drug effects / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D034341:Aristolochic Acids; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D012756:Sheep; D013094:Spermatozoa / Q000378:metabolism*; D013997:Time Factors; D020692:rab3 GTP-Binding Proteins
D034341:Aristolochic Acids; D004791:Enzyme Inhibitors; D008244:Lysophosphatidylcholines; D010455:Peptides; D010616:Phenanthrenes; C083869:rab3AL peptide; D000001:Calcimycin; D003994:Bucladesine; C000228:aristolochic acid I; D000242:Cyclic AMP; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; D002118:Calcium