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人类精卵相互作用的功能特征与蛋白质网络

Functional features and protein network of human sperm-egg interaction.

作者信息

Sabetian Soudabeh, Shamsir Mohd Shahir, Abu Naser Mohammed

机构信息

Department of Biological and Health Sciences, Faculty of Bioscience and Medical Engineering, Universiti Teknologi Malaysia , Johor , Malaysia.

出版信息

Syst Biol Reprod Med. 2014 Dec;60(6):329-37. doi: 10.3109/19396368.2014.955896. Epub 2014 Sep 15.

Abstract

Elucidation of the sperm-egg interaction at the molecular level is one of the unresolved problems in sexual reproduction, and understanding the molecular mechanism is crucial in solving problems in infertility and failed in vitro fertilization (IVF). Many molecular interactions in the form of protein-protein interactions (PPIs) mediate the sperm-egg membrane interaction. Due to the complexity of the problem such as difficulties in analyzing in vivo membrane PPIs, many efforts have failed to comprehensively elucidate the fusion mechanism and the molecular interactions that mediate sperm-egg membrane fusion. The main purpose of this study was to reveal possible protein interactions and associated molecular function during sperm-egg interaction using a protein interaction network approach. Different databases have been used to construct the human sperm-egg interaction network. The constructed network revealed new interactions. These included CD151 and CD9 in human oocyte that interact with CD49 in sperm, and CD49 and ITGA4 in sperm that interact with CD63 and CD81, respectively, in the oocyte. These results showed that the different integrins in sperm may be involved in human sperm-egg interaction. It was also suggested that sperm ADAM2 plays a role as a protein candidate involved in sperm-egg membrane interaction by interacting with CD9 in the oocyte. Interleukin-4 receptor activity, receptor signaling protein tyrosine kinase activity, and manganese ion transmembrane transport activity are the major molecular functions in sperm-egg interaction protein network. The disease association analysis indicated that sperm-egg interaction defects are also reflected in other disease networks such as cardiovascular, hematological, and breast cancer diseases. By analyzing the network, we identified the major molecular functions and disease association genes in sperm-egg interaction protein. Further experimental studies will be required to confirm the significance of these new computationally resolved interactions and the genetic links between sperm-egg interaction abnormalities and the associated disease.

摘要

在分子水平上阐明精卵相互作用是有性生殖中尚未解决的问题之一,而了解分子机制对于解决不孕不育和体外受精(IVF)失败问题至关重要。许多以蛋白质-蛋白质相互作用(PPI)形式存在的分子相互作用介导了精卵膜相互作用。由于该问题的复杂性,如体内膜PPI分析困难,许多努力都未能全面阐明融合机制以及介导精卵膜融合的分子相互作用。本研究的主要目的是使用蛋白质相互作用网络方法揭示精卵相互作用过程中可能的蛋白质相互作用及相关分子功能。已使用不同数据库构建人类精卵相互作用网络。构建的网络揭示了新的相互作用。这些相互作用包括人类卵母细胞中的CD151和CD9与精子中的CD49相互作用,以及精子中的CD49和ITGA4分别与卵母细胞中的CD63和CD81相互作用。这些结果表明,精子中不同的整合素可能参与人类精卵相互作用。还表明精子ADAM2通过与卵母细胞中的CD9相互作用,作为参与精卵膜相互作用的蛋白质候选物发挥作用。白细胞介素-4受体活性、受体信号蛋白酪氨酸激酶活性和锰离子跨膜转运活性是精卵相互作用蛋白质网络中的主要分子功能。疾病关联分析表明,精卵相互作用缺陷也反映在其他疾病网络中,如心血管疾病、血液系统疾病和乳腺癌疾病。通过分析该网络,我们确定了精卵相互作用蛋白质中的主要分子功能和疾病关联基因。需要进一步的实验研究来证实这些新的通过计算解析的相互作用的意义以及精卵相互作用异常与相关疾病之间的遗传联系。

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