PCSK4-null sperm display enhanced protein tyrosine phosphorylation and ADAM2 proteolytic processing during in vitro capacitation

Fertil Steril. 2010 Mar 1;93(4):1112-23. doi: 10.1016/j.fertnstert.2008.12.013. Epub 2009 Apr 1.


Objective: To study the molecular basis for the accelerated capacitation rate in PCSK4-null sperm.

Design: Comparative and controlled experimental research study.

Setting: Academic medical institute.

Animal(s): Male mice C57BL/6J wild-type or null congenics for the Pcsk4 allele.

Intervention(s): Cauda and epididymal sperm were capacitated for varying times.

Main outcome measure(s): Differences in sperm protein tyrosine phosphorylation and proteolytic processing of sperm-egg ligands ADAM2 and ADAM3.

Result(s): The PCSK4-null sperm proteins are hyper-tyrosine phosphorylated during capacitation. This hyperphosphorylation is dependent on protein kinase A (PKA), albumin, and calcium. There is also more ADAM2 proteolytic processing from a 46-kDa form of ADAM2 to a 27-kDa form in PCSK4-null sperm than in wild-type sperm. This processing is dependent on cholesterol efflux.

Conclusion(s): Lack of PCSK4 is associated with quantitative changes in the phosphorylation and proteolysis of sperm proteins during capacitation; therefore, alterations in signal transduction and proteolytic processing during capacitation may underlie the fertilization incompetence of PCSK4-null sperm. More investigation is needed to determine how and to what extent these changes might contribute to the loss of fertilizing ability of PCSK4-null sperm.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Fertilins
  • Humans
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism
  • Phosphorylation
  • Proprotein Convertases
  • Protein Processing, Post-Translational* / genetics
  • Serine Endopeptidases / deficiency*
  • Serine Endopeptidases / genetics
  • Sperm Capacitation* / genetics
  • Spermatozoa / metabolism*
  • Subtilisins
  • Tyrosine / metabolism*


  • Membrane Glycoproteins
  • Tyrosine
  • Peptide Hydrolases
  • Pcsk4 protein, mouse
  • Proprotein Convertases
  • Serine Endopeptidases
  • Subtilisins
  • ADAM Proteins
  • ADAM2 protein, human
  • Adam2 protein, mouse
  • Fertilins