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Home / Equine Research Bank / Biol Reprod / Guanine-nucleotide exchange factors (RAPGEF3/RAPGEF4) induce...
Biology of reproduction2011; 85(1); 179-188; doi: 10.1095/biolreprod.110.085555

Guanine-nucleotide exchange factors (RAPGEF3/RAPGEF4) induce sperm membrane depolarization and acrosomal exocytosis in capacitated stallion sperm.

Abstract: Capacitation encompasses the molecular changes sperm undergo to fertilize an oocyte, some of which are postulated to occur via a cAMP-PRKACA (protein kinase A)-mediated pathway. Due to the recent discovery of cAMP-activated guanine nucleotide exchange factors RAPGEF3 and RAPGEF4, we sought to investigate the separate roles of PRKACA and RAPGEF3/RAPGEF4 in modulating capacitation and acrosomal exocytosis. Indirect immunofluorescence localized RAPGEF3 to the acrosome and subacrosomal ring and RAPGEF4 to the midpiece in equine sperm. Addition of the RAPGEF3/RAPGEF4-specific cAMP analogue 8-(p-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8pCPT) to sperm incubated under both noncapacitating and capacitating conditions had no effect on protein tyrosine phosphorylation, thus supporting a PRKACA-mediated event. Conversely, activation of RAPGEF3/RAPGEF4 with 8pCPT induced acrosomal exocytosis in capacitated equine sperm at rates (34%) similar (P > 0.05) to those obtained in progesterone- and calcium ionophore-treated sperm. In the mouse, capacitation-dependent hyperpolarization of the sperm plasma membrane has been shown to recruit low voltage-activated T-type Ca(2+) channels, which later open in response to zona pellucida-induced membrane depolarization. We hypothesized that RAPGEF3 may be inducing acrosomal exocytosis via depolarization-dependent Ca(2+) influx, as RAPGEF3/RAPGEF4 have been demonstrated to play a role in the regulation of ion channels in somatic cells. We first compared the membrane potential (E(m)) of noncapacitated (-37.11 mV) and capacitated (-53.74 mV; P = 0.002) equine sperm. Interestingly, when sperm were incubated (6 h) under capacitating conditions in the presence of 8pCPT, E(m) remained depolarized (-32.06 mV). Altogether, these experiments support the hypothesis that RAPGEF3/RAPGEF4 activation regulates acrosomal exocytosis via its modulation of E(m), a novel role for RAPGEF3/RAPGEF4 in the series of events required to achieve fertilization.
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Publication Date: 2011-04-06 PubMed ID: 21471298PubMed Central: PMC3123385DOI: 10.1095/biolreprod.110.085555Google Scholar: Lookup
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  • Journal Article
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  • N.I.H.
  • Extramural
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  • Non-U.S. Gov't
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the role of certain proteins, RAPGEF3 and RAPGEF4, and how they influence the necessary changes sperm undergo (known as capacitation) to fertilise an oocyte (egg cell). It suggests these proteins regulate the process of acrosomal exocytosis, required for fertilisation, through control of membrane potential.

Understanding the Research

  • The main focus of the study is to explore the roles of the recently discovered proteins, RAPGEF3 and RAPGEF4, in sperm capacitation and acrosomal exocytosis.
  • Sperm capacitation refers to the biological changes a sperm cell undergoes to gain the ability to penetrate and fertilize an egg cell. It’s a crucial step in mammalian fertilization.
  • RAPGEF3 and RAPGEF4 are guanine nucleotide exchange factors which, in this context, are thought to be regulators of the processes involved in sperm capacitation.

Key Findings

  • The research identified the locations of RAPGEF3 and RAPGEF4 in equine sperm. RAPGEF3 was found in the acrosome and subacrosomal ring, and RAPGEF4 in the midpiece.
  • When the researchers activated RAPGEF3/RAPGEF4 in sperm, it induced acrosomal exocytosis at a rate similar to those obtained with other treatments. Acrosomal exocytosis refers to the release of enzymes from the acrosome, a structure in the sperm head, which helps the sperm penetrate the egg.
  • Another significant finding is the potential role of RAPGEF3/RAPGEF4 in the regulation of membrane potential (Em), the difference in voltage across a cell membrane. This observation adds a novel role to these proteins in the process of sperm capacitation and acrosomal exocytosis.
  • The study found that the membrane potential was different between noncapacitated and capacitated sperm. Interestingly, when RAPGEF3/RAPGEF4 were activated under capacitating conditions, the membrane potential remained depolarized, suggesting a role for these proteins in this process.

Conclusion and Implications

  • Given these findings, it’s suggested that RAPGEF3/RAPGEF4 play crucial and previously unidentified roles in the sequence of events that allow the sperm to achieve fertilisation.
  • This new knowledge contributes to the larger understanding of the molecular processes involved in sperm capacitation, and could guide future research and advances in fertility treatments.

Cite This Article

APA
McPartlin LA, Visconti PE, Bedford-Guaus SJ. (2011). Guanine-nucleotide exchange factors (RAPGEF3/RAPGEF4) induce sperm membrane depolarization and acrosomal exocytosis in capacitated stallion sperm. Biol Reprod, 85(1), 179-188. https://doi.org/10.1095/biolreprod.110.085555

Publication

Biology of reproduction
ISSN: 1529-7268
NlmUniqueID: 0207224
Country: United States
Language: English
Volume: 85
Issue: 1
Pages: 179-188

Researcher Affiliations

McPartlin, L A
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Visconti, P E
    Bedford-Guaus, S J

      MeSH Terms

      • Acrosome / physiology
      • Animals
      • Cyclic AMP / analogs & derivatives
      • Cyclic AMP / metabolism
      • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / antagonists & inhibitors
      • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / metabolism
      • Dichlororibofuranosylbenzimidazole / analogs & derivatives
      • Exocytosis
      • Guanine Nucleotide Exchange Factors / metabolism
      • Horses / metabolism
      • Male
      • Membrane Potentials
      • Mice
      • Phosphorylation
      • Protein-Tyrosine Kinases / metabolism
      • Signal Transduction
      • Sperm Capacitation
      • Thionucleotides

      Grant Funding

      • R01 HD038082 / NICHD NIH HHS
      • R01 HD044044 / NICHD NIH HHS
      • HD38082 / NICHD NIH HHS
      • HD44044 / NICHD NIH HHS

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