The challenges involved in elucidating the molecular basis of sperm-egg recognition in mammals and approaches to overcome them.
The challenges involved in elucidating the molecular basis of sperm-egg recognition in mammals and approaches to overcome them.
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DOI：
10.1007/s00441-015-2243-3
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发表时间：
2016-01
影响因子：
3.6
通讯作者：
Bianchi E
中科院分区：
文献类型：
--
作者：
Wright GJ;Bianchi E
有性生殖被许多不同的生物用来创造新一代的遗传上不同的后代。来自不同性别或交配类型的细胞将它们的遗传物质分离成单倍体配子，然后这些配子必须在称为受精的过程中相互识别和融合以形成二倍体合子。尽管受精至关重要，但我们对配子如何相互识别的分子机制知之甚少，特别是在哺乳动物中，尽管它们表面显示的蛋白质几乎肯定参与其中。这种知识的缺乏主要是由于哺乳动物配子（精子和卵子）的独特生物学特性，这使得它们在实验上难以操作，以及识别膜包埋的细胞表面受体蛋白之间的相互作用的技术挑战。在这篇综述中，我们将讨论我们目前对动物配子识别的认识，强调对我们的理解做出了重要贡献，为什么特定的模型系统是有帮助的，以及为什么哺乳动物的进展特别具有挑战性。我们讨论了哺乳动物体外受精和小鼠靶向基因破坏的发展是如何引发进步的重要技术进步。我们认为，采用的方法来发现细胞表面配子识别蛋白之间的新的相互作用，应占膜蛋白的不寻常的生化特性和通常的高度瞬态性质的相互作用。最后，我们描述了这些原则是如何应用到确定朱诺精子Izumo1，相互作用是必不可少的哺乳动物受精卵受体。
Sexual reproduction is used by many different organisms to create a new generation of genetically distinct progeny. Cells originating from separate sexes or mating types segregate their genetic material into haploid gametes which must then recognize and fuse with each other in a process known as fertilization to form a diploid zygote. Despite the central importance of fertilization, we know remarkably little about the molecular mechanisms that are involved in how gametes recognize each other, particularly in mammals, although the proteins that are displayed on their surfaces are almost certainly involved. This paucity of knowledge is largely due to both the unique biological properties of mammalian gametes (sperm and egg) which make them experimentally difficult to manipulate, and the technical challenges of identifying interactions between membrane-embedded cell surface receptor proteins. In this review, we will discuss our current knowledge of animal gamete recognition, highlighting where important contributions to our understanding were made, why particular model systems were helpful, and why progress in mammals has been particularly challenging. We discuss how the development of mammalian in vitro fertilization and targeted gene disruption in mice were important technological advances that triggered progress. We argue that approaches employed to discover novel interactions between cell surface gamete recognition proteins should account for the unusual biochemical properties of membrane proteins and the typically highly transient nature of their interactions. Finally, we describe how these principles were applied to identify Juno as the egg receptor for sperm Izumo1, an interaction that is essential for mammalian fertilization.