Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human spermoocyte recognition
Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human spermoocyte recognition
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DOI：
10.1093/molehr/gas064
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发表时间：
2013-03-01
影响因子：
4
通讯作者：
Nixon，Brett
中科院分区：
文献类型：
--
作者：
Redgrove，Kate A.;Anderson，Amanda L.;Nixon，Brett
哺乳动物精子的一个独特特征是，在射精后，它们无法识别并结合到排卵的卵母细胞上。这些功能属性只有在细胞上升到雌性生殖道后才能实现，在此过程中，它们经历了无数的生化和生物物理变化，统称为“获能”。我们以前已经证明，这种功能转变部分是通过改变精子表面结构来实现的，从而导致多聚体精子-卵母细胞受体复合体的组装和/或呈递。在这项研究中，我们通过表征一个含有芳基硫酸酯酶A(ARSA)、精子黏附分子1(SPAM1)和分子伴侣热休克70 kDa蛋白2(HSPA2)的复合体来扩展我们的发现。通过应用流式细胞术，我们发现该复合体经历了与获能相关的易位，以促进ARSA重新定位到人类精子头部的顶端区域，这一位置与精子-透明带(ZP)相互作用的中介作用相一致。相反，SPAM1似乎重新定位远离精子表面，可能反映了它在精子-ZP识别之前对卵丘基质扩散的主要作用。在外源性胆固醇或广谱蛋白激酶A(PKA)和酪氨酸激酶抑制剂中孵育获能精子后，该复合体的戏剧性移位被完全取消，这表明这可能是由于膜流动性特征的改变，同时也是由获能相关的信号转导通路的激活所驱动的。总而言之，这些数据为人类精子中多聚体蛋白复合体的亚细胞定位和潜在功能提供了新的见解。
A unique characteristic of mammalian spermatozoa is that, upon ejaculation, they are unable to recognize and bind to an ovulated oocyte. These functional attributes are only realized following the cells' ascent of the female reproductive tract whereupon they undergo a myriad of biochemical and biophysical changes collectively referred to as ‘capacitation’. We have previously shown that this functional transformation is, in part, engineered by the modification of the sperm surface architecture leading to the assembly and/or presentation of multimeric sperm–oocyte receptor complexes. In this study, we have extended our findings through the characterization of one such complex containing arylsulfatase A (ARSA), sperm adhesion molecule 1 (SPAM1) and the molecular chaperone, heat shock 70kDa protein 2 (HSPA2). Through the application of flow cytometry we revealed that this complex undergoes a capacitation-associated translocation to facilitate the repositioning of ARSA to the apical region of the human sperm head, a location compatible with a role in the mediation of sperm–zona pellucida (ZP) interactions. Conversely, SPAM1 appears to reorient away from the sperm surface, possibly reflecting its primary role in cumulus matrix dispersal preceding sperm–ZP recognition. The dramatic relocation of the complex was completely abolished by incubation of capacitating spermatozoa in exogenous cholesterol or broad spectrum protein kinase A (PKA) and tyrosine kinase inhibitors suggesting that it may be driven by alterations in membrane fluidity characteristics and concurrently by the activation of a capacitation-associated signal transduction pathway. Collectively these data afford novel insights into the sub-cellular localization and potential functions of multimeric protein complexes in human spermatozoa.