Cyclic AMP signalling during mammalian sperm capacitation -: Still largely Terra incognita

Cyclic AMP signalling during mammalian sperm capacitation -: Still largely Terra incognita
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DOI:
10.1046/j.1439-0531.2003.00400.x
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发表时间:
2003-04-01
影响因子:
1.7
通讯作者:
Harrison, RAP
Harrison, RAP
中科院分区:
农林科学3区
文献类型:
--
作者:
Harrison, RAP

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已知在哺乳动物精子获能过程中,cAMP在细胞内信号转导中发挥重要作用。然而,尽管有很多研究,但环状AMP参与的许多分子细节仍然不清楚。在这篇综述中,我讨论了以下几个方面,提供了一些原始数据作为相关的说明。关于环状AMP的合成,精子中存在的腺酰环化酶的形式的数量、它们是胞浆的还是与亚细胞结构结合的、以及它们对哪些生理效应因子(如重碳酸盐、钙离子或受体偶联的G-蛋白)的反应存在不确定性。虽然精子细胞内环磷酸腺苷的净水平取决于腺酰环化酶和磷酸二酯酶的相对活性,但不同物种之间在基础水平和环化酶激活后(如用碳酸氢盐处理精子后)的水平上都有很大的差异。此外,整体环状AMP水平的微小变化可以导致环状AMP依赖功能的大变化。最后,尽管环磷酸腺苷水平对小苏打和钙离子(获能介质的关键成分)等效应物处理精子的反应非常迅速,但功能反应率之间存在很大差异。例如,运动能力的增强和磷脂不对称性的崩溃在几分钟内就会发生,而获得能力的条件下需要超过1小时的暴露,才能检测到依赖于AMP的蛋白酪氨酸磷酸化或精子数量达到获能状态。
Cyclic AMP is known to play a major role in intracellular signalling during mammalian sperm capacitation. However, despite much research, many of the molecular details of cyclic AMP's involvement remain obscure. In this review, I discuss the following aspects, presenting some original data as illustration where relevant. With respect to cyclic AMP synthesis, uncertainties exist as to the number of forms of adenylyl cyclase that are present in the spermatozoon, whether they are cytosolic or bound to subcellular structures, and which physiological effectors they respond to (e.g. bicarbonate, Ca2+, or receptor-coupled G-proteins). While net intracellular levels of cyclic AMP in spermatozoa depend upon the relative activities of adenylyl cyclase and phosphodiesterase, there are wide between-sample variations within species, both in basal levels and in levels attained after activation of the cyclase (e.g. after sperm treatment with bicarbonate). Moreover, minor changes in bulk cyclic AMP levels can result in large changes in cyclic AMP-dependent functions. Finally, while cyclic AMP levels respond very rapidly to sperm treatment by effectors such as bicarbonate and Ca2+ (key components of capacitating media), there are big discrepancies between the rates of functional response. For example, enhancement of motility and collapse of phospholipid asymmetry take place within a few minutes, whereas more than 1 h of exposure to capacitating conditions is needed for cyclic AMP-dependent protein tyrosine phosphorylation to become detectable or for the sperm population to attain a capacitated state.