The molecular chaperone HSPA2 plays a key role in regulating the expression of sperm surface receptors that mediate sperm-egg recognition.
The molecular chaperone HSPA2 plays a key role in regulating the expression of sperm surface receptors that mediate sperm-egg recognition.
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DOI：
10.1371/journal.pone.0050851
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Aitken RJ
中科院分区：
文献类型：
--
作者：
Redgrove KA;Nixon B;Baker MA;Hetherington L;Baker G;Liu DY;Aitken RJ
男性不育症患者精子中常见的缺陷是特发性精卵识别失败。为了解决这种情况下的分子基础，我们比较了精子的蛋白质组学的档案表现出受损的精子-卵子识别能力与正常细胞使用无标记质谱（MS）为基础的定量。该分析表明，受损的精子结合与精子蛋白质组中分子伴侣热休克70 kDa蛋白2（HSPA 2）的表达减少有关。蛋白质印迹分析证实了这一观察结果在独立的患者，并证明该缺陷并没有扩展到其他成员的HSP 70家族。HSPA 2作为5种大分子量复合物的主要成分存在于人类精子的顶体结构域中，其中最主要的是发现含有与另外两种蛋白质密切相关的HSPA 2，精子粘附分子1（SPAM 1）和芳基硫酸酯酶A（ARSA），这两种蛋白质先前都与精卵相互作用有关。SPAM 1，ARSA和HSPA 2之间的相互作用在一个多聚体复合物介导的精子-卵子相互作用，再加上这个过程的完全失败时，HSPA 2是耗尽不育患者，提供了新的见解精子功能受损的男性不育症的情况下的机制。
A common defect encountered in the spermatozoa of male infertility patients is an idiopathic failure of sperm–egg recognition. In order to resolve the molecular basis of this condition we have compared the proteomic profiles of spermatozoa exhibiting an impaired capacity for sperm-egg recognition with normal cells using label free mass spectrometry (MS)-based quantification. This analysis indicated that impaired sperm–zona binding was associated with reduced expression of the molecular chaperone, heat shock 70 kDa protein 2 (HSPA2), from the sperm proteome. Western blot analysis confirmed this observation in independent patients and demonstrated that the defect did not extend to other members of the HSP70 family. HSPA2 was present in the acrosomal domain of human spermatozoa as a major component of 5 large molecular mass complexes, the most dominant of which was found to contain HSPA2 in close association with just two other proteins, sperm adhesion molecule 1 (SPAM1) and arylsulfatase A (ARSA), both of which that have previously been implicated in sperm-egg interaction. The interaction between SPAM1, ARSA and HSPA2 in a multimeric complex mediating sperm-egg interaction, coupled with the complete failure of this process when HSPA2 is depleted in infertile patients, provides new insights into the mechanisms by which sperm function is impaired in cases of male infertility.
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影响因子：
3.6
作者：
De Iuliis, Geoffry N.;Thomson, Laura K.;Aitken, R. John
通讯作者：
Aitken, R. John
影响因子：
--
作者：
Dubé, C;Leclerc, P;Bailey, JL
通讯作者：
Bailey, JL
影响因子：
2.7
作者：
Carmona, E;Weerachatyanukul, W;Tanphaichitr, N
通讯作者：
Tanphaichitr, N
影响因子：
4.8
作者：
Baba, D;Kashiwabara, SI;Baba, T
通讯作者：
Baba, T
影响因子：
6.1
作者：
Hammoud, Saher Sue;Nix, David A.;Carrell, Douglas T.
通讯作者：
Carrell, Douglas T.