Protein kinase A inhibition induces EPAC-dependent acrosomal exocytosis in human sperm / 亚洲男科学杂志(英文版)
Asian Journal of Andrology
; (6): 337-344, 2019.
Article
in En
| WPRIM
| ID: wpr-1009691
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ABSTRACT
To interact with the egg, the spermatozoon must undergo several biochemical and motility modifications in the female reproductive tract, collectively called capacitation. Only capacitated sperm can undergo acrosomal exocytosis, near or on the egg, a process that allows the sperm to penetrate and fertilize the egg. In the present study, we investigated the involvement of cyclic adenosine monophosphate (cAMP)-dependent processes on acrosomal exocytosis. Inhibition of protein kinase A (PKA) at the end of capacitation induced acrosomal exocytosis. This process is cAMP-dependent; however, the addition of relatively high concentration of the membrane-permeable 8-bromo-cAMP (8Br-cAMP, 0.1 mmol l-1) analog induced significant inhibition of the acrosomal exocytosis. The induction of acrosomal exocytosis by PKA inhibition was significantly inhibited by an exchange protein directly activated by cAMP (EPAC) ESI09 inhibitor. The EPAC selective substrate activated AE at relatively low concentrations (0.02-0.1 μmol l-1), whereas higher concentrations (>5 μmol l-1) were inhibitory to the AE induced by PKA inhibition. Inhibition of PKA revealed about 50% increase in intracellular cAMP levels, conditions under which EPAC can be activated to induce the AE. Induction of AE by activating the actin severing-protein, gelsolin, which causes F-actin dispersion, was inhibited by the EPAC inhibitor. The AE induced by PKA inhibition was mediated by phospholipase C activity but not by the Ca2+-channel, CatSper. Thus, inhibition of PKA at the end of the capacitation process induced EPAC/phospholipase C-dependent acrosomal exocytosis. EPAC mediates F-actin depolymerization and/or activation of effectors downstream to F-actin breakdown that lead to acrosomal exocytosis.
Key words
Full text:
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Index:
WPRIM
Main subject:
Spermatozoa
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Acrosome
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8-Bromo Cyclic Adenosine Monophosphate
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Signal Transduction
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Calcimycin
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Cyclic AMP-Dependent Protein Kinases
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Cyclic AMP
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Thapsigargin
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Acrosome Reaction
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Guanine Nucleotide Exchange Factors
Limits:
Humans
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Male
Language:
En
Journal:
Asian Journal of Andrology
Year:
2019
Type:
Article