精子
细胞生物学
舍宾
毛皮
生物
前蛋白转化酶
丝氨酸蛋白酶
凝集素
前蛋白转化酶类
生物化学
附睾
化学
蛋白酶
酶
遗传学
脂蛋白
胆固醇
细胞凋亡
基因
低密度脂蛋白受体
作者
Prashant Mishra,Qing Qiu,Andrée Gruslin,Yuji Hidaka,Majambu Mbikay,Ajoy Basak
出处
期刊:Current Molecular Medicine
[Bentham Science]
日期:2012-08-01
卷期号:12 (8): 1050-1067
被引量:6
标识
DOI:10.2174/156652412802480961
摘要
PC4 or PCSK4 belongs to the 9-member superfamily of mammalian subtilases collectively called Proprotein Convertases or Proprotein Convertase Subtilisin/Kexins that convert inactive precursor proteins into their active mature forms by endoproteolytic cleavage. PC4-activity plays a crucial role in mammalian fertilization via activation of sperm surface proteins. PC4 knockout mice exhibit severely impaired male fertility due to premature sperm acrosome reaction. Regulation of sperm-PC4 activity during its storage and transport through epididymis is an important determinant for ultimate egg-binding and fertilizing capacities of sperms. Herein we show that epididymal serpin CRES (cystatin related epididymal spermatogenic) recombinant protein inhibits PC4 activity in vitro in a differential manner when measured against the fluorogenic substrate Boc- RVRR-MCA depending on its oligomeric state. Thus while CRES-dimer exhibits K(i) ∼8 μM, the corresponding monomer showed K(i) > 100 μM. Both forms also blocked PC4-mediated processing of human proIGF-2 in human placenta tropoblast cell line with dimer being more efficient. Using specific inhibitors and substrates, we also demonstrated the presence of PC4-like activity and CRES protein in varying levels in the fluids of various epididymal compartments. Our observations suggest a potential function of CRES as a regulator of PC4 in sperm-egg interaction and fertilization.
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