Role and regulation of intracellular calcium in acrosomal exocytosis
Role and regulation of intracellular calcium in acrosomal exocytosis
复制标题
DOI：
10.1016/s0165-0378(01)00085-7
复制
发表时间：
2002-01-01
影响因子：
3.4
通讯作者：
Breitbart, H
中科院分区：
文献类型：
--
作者：
Breitbart, H
哺乳动物精子顶体反应需要钙流入，顶体反应是与卵子结合后在精子头部发生的胞吐事件。在这种结合之前，精子在女性生殖道中经历一系列生化转变，统称为获能。获能过程中的第一个事件是细胞内钙、碳酸氢盐和过氧化氢的升高，它们共同激活腺苷酸环化酶产生环-AMP，从而激活蛋白激酶A。在获能期间，膜结合磷脂酶C增加，并且通过向细胞中添加表皮生长因子来高度刺激这种结合。我们认为透明带至少与精子头部质膜中的两种不同受体结合。一种是 G(i) 偶联受体，可以激活磷脂酶 C beta (1)，并可能调节腺苷酸环化酶以进一步提高环 AMP 水平。环 AMP 激活蛋白激酶 A，打开顶体外膜中的钙通道，导致胞质钙相对较小的升高。 Ca2+ 的增加导致磷脂酶 C γ 的激活。它与第二个酪氨酸激酶受体偶联。磷脂酶C活性的产物二酰甘油和三磷酸肌醇(IP3)将导致蛋白激酶C(PKC)和IP3受体的激活。 PKC 将打开质膜中的钙通道，IP3 将激活顶体外膜中的钙通道，导致胞质钙的更高增加。此外，顶体中钙的消耗将激活钙池操纵的Ca2+通道，导致胞浆钙快速增加（300 500 nM），导致膜融合并完成顶体反应。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
Calcium influx is required for the mammalian sperm acrosome reaction, an exocytotic event occurring in the sperm head after binding to the egg. Prior to this binding, the spermatozoon undergo, in the female reproductive tract, a series of biochemical transformations, collectively called capacitation. The first event in capacitation is the elevation of intracellular calcium, bicarbonate and hydrogen peroxide, which collectively activate adenylyl cyclase to produce cyclic-AMP, which activates protein kinase A. During capacitation, there is an increase in the membrane-bound phospholipase C, and this binding is highly stimulated by adding epidermal growth factor to the cells. We suggest that zona-pellucida binds to at least two different receptors in the sperm head plasma membrane. One is a G(i)-coupled receptor that can activate phospholipase C beta (1) and might regulate adenylyl cyclase to further enhance cyclic-AMP levels. The cyclic AMP activates protein kinase A to open a calcium channel in the outer acrosomal membrane, resulting in a relatively small rise in cytosolic calcium. This rise in Ca2+ leads to activation of phospholipase C gamma. which is coupled to the second tyrosine kinase receptor. The products of phospholipase C activity, diacylglycerol and inositol-trisphosphate (IP3), will lead to activation of protein kinase C (PKC) and IP3-receptor. PKC will open a calcium channel in the plasma membrane and IP3 will activate the calcium channel in the outer acrosomal membrane, leading to a higher increase in cytosolic calcium. In addition, the depletion of calcium in the acrosome will activate a store-operated Ca2+ channel, resulting in a very fast increase in cytosolic calcium (300 500 nM), leading to membrane fusion and completing the acrosome reaction. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.