Deparment of Biology, McGill University, Montreal, Quebec, Canada.
Reproduction. 2010 Nov;140(5):673-84. doi: 10.1530/REP-09-0545. Epub 2010 Aug 17.
Research on fertilization in mammalian species has revealed that Ca(2+) is an important player in biochemical and physiological events enabling the sperm to penetrate the oocyte. Ca(2+) is a signal transducer that particularly mediates capacitation and acrosome reaction (AR). Before becoming fertilization competent, sperm must experience several molecular, biochemical, and physiological changes where Ca(2+) plays a pivotal role. Calpain-1 and calpain-2 are Ca(2+)-dependent proteases widely studied in mammalian sperm; they have been involved in capacitation and AR but little is known about their mechanism. In this work, we establish the association of calpastatin with calpain-1 and the changes undergone by this complex during capacitation in guinea pig sperm. We found that calpain-1 is relocated and translocated from cytoplasm to plasma membrane (PM) during capacitation, where it could cleave spectrin, one of the proteins of the PM-associated cytoskeleton, and facilitates AR. The aforementioned results were dependent on the calpastatin phosphorylation and the presence of extracellular Ca(2+). Our findings underline the contribution of the sperm cytoskeleton in the regulation of both capacitation and AR. In addition, our findings also reveal one of the mechanisms by which calpain and calcium exert its function in sperm.
哺乳动物物种受精的研究表明，Ca(2+) 是使精子穿透卵母细胞的生化和生理事件中的重要参与者。Ca(2+) 是一种信号转导物，特别介导顶体反应（AR）和获能。在具有受精能力之前，精子必须经历几个分子、生化和生理变化，其中 Ca(2+) 起着关键作用。钙蛋白酶-1 和钙蛋白酶-2 是哺乳动物精子中广泛研究的 Ca(2+)-依赖性蛋白酶；它们已参与获能和 AR，但对其机制知之甚少。在这项工作中，我们建立了钙蛋白酶抑制剂-1 与钙蛋白酶-1 的关联，并研究了该复合物在豚鼠精子获能过程中的变化。我们发现钙蛋白酶-1 在获能过程中从细胞质重新定位并转位到质膜（PM），在那里它可以切割质膜相关细胞骨架的蛋白之一血影蛋白，从而促进 AR。上述结果依赖于钙蛋白酶抑制剂-1 的磷酸化和细胞外 Ca(2+) 的存在。我们的发现强调了精子细胞骨架在调节获能和 AR 中的作用。此外，我们的发现还揭示了钙蛋白酶和钙在精子中发挥功能的一种机制。
