Chronic Disease Program, Ottawa Health Research Institute, Ottawa, Ontario, Canada.
Fertil Steril. 2010 Mar 1;93(4):1112-23. doi: 10.1016/j.fertnstert.2008.12.013. Epub 2009 Apr 1.
To study the molecular basis for the accelerated capacitation rate in PCSK4-null sperm.
Comparative and controlled experimental research study.
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.
研究 PCSK4 缺失精子加速获能率的分子基础。
对比性和控制性实验研究。
学术医学研究所。
C57BL/6J 野生型或 Pcsk4 等位基因缺失纯合子的雄性小鼠。
对尾和附睾精子进行不同时间的获能处理。
精子蛋白酪氨酸磷酸化和精子卵结合配体 ADAM2 和 ADAM3 的蛋白水解加工的差异。
PCSK4 缺失精子在获能过程中表现出过度的酪氨酸磷酸化。这种过度磷酸化依赖于蛋白激酶 A（PKA）、白蛋白和钙。PCSK4 缺失精子中的 ADAM2 也有更多的蛋白水解加工，从 ADAM2 的 46kDa 形式转化为 27kDa 形式，而野生型精子中则没有。这种加工依赖于胆固醇外流。
缺乏 PCSK4 与获能过程中精子蛋白磷酸化和蛋白水解的定量变化有关；因此，获能过程中信号转导和蛋白水解加工的改变可能是 PCSK4 缺失精子受精能力丧失的基础。需要进一步研究以确定这些变化如何以及在多大程度上可能导致 PCSK4 缺失精子丧失受精能力。
