title: PCSK4-null sperm display enhanced protein tyrosine phosphorylation and ADAM2 proteolytic processing during in vitro capacitation.
abstract: OBJECTIVE
  To study the molecular basis for the accelerated capacitation rate in PCSK4-null sperm.
  
  
  METHODS
  Comparative and controlled experimental research study.
  
  
  METHODS
  Academic medical institute.
  
  
  METHODS
  Male mice C57BL/6J wild-type or null congenics for the Pcsk4 allele.
  
  
  METHODS
  Cauda and epididymal sperm were capacitated for varying times.
  
  
  METHODS
  Differences in sperm protein tyrosine phosphorylation and proteolytic processing of sperm-egg ligands ADAM2 and ADAM3.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Chronic Disease Program, Ottawa Health Research Institute, Ottawa, Ontario, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Gyamera-Acheampong
authors.forename: Julian
authors.initials: J
authors.lastname: Vasilescu
authors.forename: Daniel
authors.initials: D
authors.lastname: Figeys
authors.forename: Majambu
authors.initials: M
authors.lastname: Mbikay