Involvement of Protein Kinase A and A Kinase Anchoring Protein in the Progesterone-Initiated Human Sperm Acrosome Reaction1

2000/03/01 by D.A. Harrison, Douglas A. Harrison, Daniel W. Carr +3 · 9 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Reproductive Biology and Fertility #Sperm and Testicular Function #Reproductive biology and impacts on aquatic species

paper · pdf · doi:10.1095/biolreprod62.3.811

Abstract

The signal transduction pathways involved in the progesterone (P(4))-initiated mammalian sperm acrosome reaction (AR) are not fully understood. To investigate the role of the protein kinase A (PKA) pathway in the P(4)-initiated AR, we probed this pathway by pretreating capacitated human sperm with reagents designed to either inhibit PKA activation or disrupt PKA/A kinase anchoring protein (AKAP) interactions. Preincubation with the stearated (membrane permeable) PKA inhibitor, PKI alpha 5-24 (S-PKI alpha 5-24), significantly inhibited the P(4)-initiated AR at 10 microM as compared to stearated control peptide. In contrast, preincubation with 100 microM nonstearated PKI alpha 5-24 did not significantly inhibit versus solvent control. Preincubation with the PKA inhibitor Rp-8-Br-cAMP at 500 microM and 150 microM significantly inhibited the P(4)-initiated AR versus 8-Br-cAMP and versus solvent. Preincubation with the anchoring inhibitory peptide S-Ht-31 significantly stimulated the P(4)-initiated AR at 10, 3, and 1 microM versus inactive control peptide. The stimulation of the P(4)-initiated AR by 3 microM S-Ht31 was significantly inhibited by the addition of 30 microM S-PKI alpha 5-24 prior to the addition of S-Ht31. Preincubation with S-PKI alpha 5-24 (30 microM) partially inhibited the ionomycin (50 microM)-initiated AR. A role for PKA in the P(4)-initiated AR may exist both upstream and downstream of Ca(2+) entry. Our studies present the first evidence for the participation of PKA in the P(4)-initiated AR and also suggest that AKAPs are involved in the PKA-mediated events.

Cited by

• Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking and long term synaptic depression. [europepmc]
• Dissociation between AKAP3 and PKARII promotes AKAP3 degradation in sperm capacitation. [europepmc]
• Central role of soluble adenylyl cyclase and cAMP in sperm physiology. [europepmc]
• Non-genomic regulation and disruption of spermatozoal in vitro hyperactivation by oviductal hormones. [europepmc]
• Progesterone-enhanced sperm hyperactivation through IP 3 -PKC and PKA signals. [europepmc]
• Molecular Basis of Human Sperm Capacitation. [europepmc]
• Protein Kinase A (PRKA) Activity Is Regulated by the Proteasome at the Onset of Human Sperm Capacitation. [europepmc]
• Progesterone-Induced Sperm Release from the Oviduct Sperm Reservoir. [europepmc]
• Enhancement of rat spermatozoal hyperactivation by progesterone. [europepmc]

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