Saling P M
Oxf Rev Reprod Biol. 1989;11:339-88.
One conclusion that may be drawn from the foregoing discussion is that examination of mammalian gamete interaction at a molecular level is underway. As yet, however, it would be premature to suggest a detailed molecular model to account fully for acrosomal exocytosis. Too many possibilities exist at present, not just for sperm but for virtually all other exocytotic systems studied. It is evident, however, that many elements of typical signal transduction pathways are present in sperm, and recent work supports the idea that such pathways may be used in AR triggering. Investigations at the cellular level provide sufficient data to formulate a sequence of gamete interactions that may apply generally to mammals. This sequence is summarized in Fig. 8.2. It is suggested that the cumulus ECM functions to restrict access of only primed (i.e., capacitated) sperm to the egg. Those sperm that undergo a spontaneous AR in the midst of the cumulus ECM are prevented from further participation in fertilization by adherence to cumulus cells. Thus, a select population of capacitated, acrosome-intact sperm arrive at the zona pellucida surface under the normal conditions of fertilization. Binding to the zona pellucida is initiated by plasma membrane receptors interacting with ZP3. This primary binding results in receptor clustering, which itself is the triggering event for acrosomal exocytosis. The signal is transmitted intracellularly via G proteins to effect fusion between the plasma and outer acrosomal membranes. As a result, proacrosin is exposed. Direct evidence for specific use of ZP2 in secondary binding has not yet been reported, but is inferred from results with mouse (Bleil and Wassarman 1986), and procine (Brown and Jones 1987; Jones et al. 1988; Topfer-Petersen and Henschen 1987, 1988) gametes. This secondary binding between ZP2 and proacrosin occurs together with pH-dependent autoactivation of proacrosin to acrosin. Limited proteolysis of the zona pellucida matrix by acrosin causes digestion and increases the affinity of freshly exposed proacrosin for the zona pellucida. This cycle continues, eventually generating the narrow penetration slit through the zona pellucida. Undoubtedly, other factors are at play here, particularly motility, and it is assumed that vigorously active ('hyperactive') sperm are the cells that participate in these events. This scheme can account for the many diverse observations made in different species if two factors, kinetics and affinity, are considered. In some species, FTU aggregation may occur spontaneously at a rate faster than in others, leading to a higher level of spontaneously acrosome-reacted sperm.(ABSTRACT TRUNCATED AT 400 WORDS)
从上述讨论中可以得出的一个结论是，对哺乳动物配子相互作用的分子水平研究正在进行。然而，就目前而言，提出一个详细的分子模型以充分解释顶体胞吐作用还为时过早。目前存在太多可能性，不仅是精子，实际上对于所有其他研究过的胞吐系统都是如此。然而，很明显典型信号转导途径的许多元件存在于精子中，并且最近的研究支持这样的观点，即这些途径可能用于触发顶体反应（AR）。细胞水平的研究提供了足够的数据来制定一系列可能普遍适用于哺乳动物的配子相互作用顺序。这个顺序总结在图8.2中。有人提出，卵丘细胞外基质（ECM）的作用是限制只有已获能（即具备受精能力）的精子接近卵子。那些在卵丘细胞外基质中自发发生顶体反应的精子会因黏附在卵丘细胞上而无法进一步参与受精。因此，在正常受精条件下，一群经过筛选的具备受精能力、顶体完整的精子到达透明带表面。与透明带的结合是由质膜受体与ZP3相互作用启动的。这种初始结合导致受体聚集，而受体聚集本身就是顶体胞吐作用的触发事件。信号通过G蛋白在细胞内传递，以实现质膜与顶体外膜之间的融合。结果，前顶体蛋白酶原被暴露出来。虽然尚未有关于ZP2在二次结合中具体作用的直接证据报道，但从小鼠（Bleil和Wassarman，1986年）以及猪（Brown和Jones，1987年；Jones等人，1988年；Topfer-Petersen和Henschen，1987年、1988年）配子的研究结果中可以推断出来。ZP2与前顶体蛋白酶原之间的这种二次结合与前顶体蛋白酶原在pH依赖下自动激活为顶体蛋白酶同时发生。顶体蛋白酶对透明带基质的有限蛋白水解作用导致消化，并增加新暴露的前顶体蛋白酶原对透明带的亲和力。这个循环持续进行，最终在透明带中形成狭窄的穿透缝隙。毫无疑问，这里还有其他因素在起作用，特别是运动能力，并且假定活力旺盛（“超活化”）的精子是参与这些事件的细胞。如果考虑动力学和亲和力这两个因素，这个模式可以解释在不同物种中观察到的许多不同现象。在某些物种中，FTU聚集可能比其他物种更快地自发发生，导致自发发生顶体反应的精子水平更高。（摘要截选至400字）
