Nixon B, Lu Q, Wassler M J, Foote C I, Ensslin M A, Shur B D
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Cells Tissues Organs. 2001;168(1-2):46-57. doi: 10.1159/000016805.
Gamete recognition has been studied extensively in the mouse. In this system, it is generally believed that sperm bind to a class of O-linked oligosaccharides on the zona pellucida glycoprotein, ZP3. The best characterized sperm receptor for ZP3 is beta1, 4-galactosyltransferase (GalT), which functions in a lectin-like capacity by binding to N-terminal N-acetylglucosamine residues on ZP3 oligosaccharides. Multivalent oligosaccharides on ZP3, as well as synthetic polymers terminating in N-acetylglucosamine aggregate GalT, leading to activation of a heterotrimeric G protein cascade and culminating in the acrosome reaction. Following fertilization, cortical granules release N-acetylglucosaminidase, which removes the binding site for sperm GalT and facilitates the zona block to polyspermic binding. Genetic manipulation of GalT expression has confirmed its function as a ZP3 receptor. Overexpressing GalT on sperm leads to increased binding of ZP3, increased G protein activation, and precocious acrosome reactions. In contrast, sperm from mice made null for GalT by homologous recombination are refractory to ZP3, in that they are unable to bind soluble ZP3 and fail to undergo the acrosome reaction in response to zona glycoproteins. Surprisingly, GalT null sperm still bind to the zona and achieve low rates of fertilization in vitro. This then suggests that sperm-egg binding involves receptor-ligand interactions independent of GalT and ZP3. The current model suggests that GalT functions as the ZP3 receptor that is responsible for inducing the acrosome reaction, whereas initial sperm-zona binding is dictated by other sperm surface receptors. Consistent with this, at least three other zona pellucida monosaccharides have been implicated in sperm binding, and novel sperm surface glycoproteins have been suggested to function in gamete binding. A large scaffolding protein has been identified that associates with the GalT cytoplasmic domain and may be responsible for orchestrating its signal transduction capacities that lead to the acrosome reaction.
配子识别在小鼠中已得到广泛研究。在这个系统中，人们普遍认为精子与透明带糖蛋白ZP3上的一类O-连接寡糖结合。目前已明确的ZP3最佳精子受体是β1,4-半乳糖基转移酶（GalT），它通过与ZP3寡糖上的N-末端N-乙酰葡糖胺残基结合，以类似凝集素的方式发挥作用。ZP3上的多价寡糖以及以N-乙酰葡糖胺结尾的合成聚合物会聚集GalT，导致异源三聚体G蛋白级联反应的激活，并最终引发顶体反应。受精后，皮质颗粒释放N-乙酰葡糖胺酶，该酶会去除精子GalT的结合位点，并促进对多精受精的透明带阻断。对GalT表达的基因操作已证实其作为ZP3受体的功能。在精子上过度表达GalT会导致与ZP3的结合增加、G蛋白激活增加以及早熟顶体反应。相反，通过同源重组使GalT基因缺失的小鼠精子对ZP3不敏感，因为它们无法结合可溶性ZP3，并且对透明带糖蛋白不发生顶体反应。令人惊讶的是，GalT基因缺失的精子仍能与透明带结合，并在体外实现低受精率。这表明精子 - 卵子结合涉及独立于GalT和ZP3的受体 - 配体相互作用。当前模型表明，GalT作为负责诱导顶体反应的ZP3受体，而最初的精子 - 透明带结合则由其他精子表面受体决定。与此一致的是，至少还有三种其他透明带单糖与精子结合有关，并且已提出新的精子表面糖蛋白在配子结合中发挥作用。已鉴定出一种大型支架蛋白，它与GalT细胞质结构域相关联，可能负责协调其导致顶体反应的信号转导能力。
