Investigation of the expression and functional significance of the novel mouse sperm protein, a disintegrin and metalloprotease with thrombospondin type 1 motifs number 10 (ADAMTS10)
Investigation of the expression and functional significance of the novel mouse sperm protein, a disintegrin and metalloprotease with thrombospondin type 1 motifs number 10 (ADAMTS10)
复制标题
DOI：
10.1111/j.1365-2605.2011.01235.x
复制
发表时间：
2012-08-01
影响因子：
--
通讯作者：
Nixon, B.
中科院分区：
文献类型：
--
作者：
Dun, M. D.;Anderson, A. L.;Nixon, B.
受精代表了雄配子和雌配子之间一系列复杂相互作用的顶峰。尽管我们的理解取得了进展，但这些基本相互作用背后的确切分子机制在很大程度上仍未确定。然而，越来越多的人认识到，这一过程需要多个精子受体的协同作用，这些受体与互补的透明带配体和位于卵膜表面的精子受体具有亲和力。在与受精有关的候选精子蛋白中，属于ADAM(一种去整合素和金属蛋白酶)家族的蛋白受到了相当大的关注。这里描述的研究的重点一直是该蛋白酶家族中密切相关的成员ADAMTS10的特征，ADAMTS10是一种去整合素和金属蛋白酶，具有血栓反应蛋白1型基序编号10)。我们已经证明，ADAMTS10在小鼠精子发生的后期表达，并被整合到发育中的精子细胞的顶体区域。在精子成熟过程中，这种蛋白质在头部顶体周围区域的表面表达之前似乎经过了加工。我们的集体数据表明，从这个位置，ADAMTS10参与了精子与透明带的黏附。事实上，将获能精子与金属蛋白酶活性的广谱抑制剂Galardin或抗ADAMTS10抗血清预先孵育后，它们参与小带粘连的能力显著降低。总体而言，这些研究支持这样的观点，即精母细胞相互作用涉及相当多的功能冗余，并确定ADAMTS10是调节这些根本重要事件的新候选。
Fertilization represents the culmination of a series of complex interactions between male and female gametes. Despite advances in our understanding, the precise molecular mechanisms underlying these fundamental interactions remain largely uncharacterized. There is however growing recognition that this process requires the concerted action of multiple sperm receptors that possess affinity for complementary zona pellucida ligands and those that reside on the surface of the oolemma. Among the candidate sperm proteins that have been implicated in fertilization, those belonging to the ADAM (a disintegrin and metalloprotease) family of proteases have received considerable attention. The focus of the studies described herein has been the characterization of a closely related member of this protease family, ADAMTS10 (a disintegrin and metalloprotease with thrombospondin type 1 motifs number 10). We have demonstrated that ADAMTS10 is expressed during the later stages of mouse spermatogenesis and incorporated into the acrosomal domain of developing spermatids. During sperm maturation, the protein appears to be processed before being expressed on the surface of the peri-acrosomal region of the head. Our collective data suggest that, from this position, ADAMTS10 participates in sperm adhesion to the zona pellucida. Indeed, pre-incubation of capacitated spermatozoa with either galardin, a broad spectrum inhibitor of metalloprotease activity, or anti-ADAMTS10 antisera elicited a significant reduction in their ability to engage in zona adhesion. Overall, these studies support the notion that spermoocyte interactions involve considerable functional redundancy and identify ADAMTS10 as a novel candidate in the mediation of these fundamentally important events.