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

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 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.

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