Cystatin-Related Epididymal Spermatogenic Aggregates in the Epididymis
Cystatin-Related Epididymal Spermatogenic Aggregates in the Epididymis
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DOI：
10.2164/jandrol.111.012963
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发表时间：
2011-11-01
影响因子：
--
通讯作者：
Whelly, Sandra
中科院分区：
文献类型：
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作者：
Cornwall, Gail A.;von Horsten, H. Henning;Whelly, Sandra
胱氨酸蛋白酶抑制剂相关的附睾精子发生（克雷斯）是半胱氨酸蛋白酶抑制剂超家族中第2家族半胱氨酸蛋白酶抑制剂的生殖亚组的定义成员。克雷斯由附睾起始段合成和分泌，存在于精子顶体中，提示其在精子成熟和受精中的作用。我们以前已经证明，克雷斯是作为单体（14和N-糖基化19 kd的形式）以及十二烷基硫酸钠敏感和十二烷基硫酸钠抗性的高分子量复合物存在于附睾腔内。我们还发现，重组克雷斯蛋白在体外会自我聚集并形成淀粉样结构，这提高了ORES在体内也可能形成淀粉样结构的可能性。淀粉样蛋白是一种具有特定交叉β折叠结构的大蛋白质聚集体，其存在通常与疾病相关。这篇综述讨论了附睾中的蛋白质聚集，并提供了淀粉样蛋白形成的简要概述，包括最近在其他器官系统中识别非病理性淀粉样蛋白并执行生物学功能（即功能性淀粉样蛋白）的研究。还描述了为确定淀粉样蛋白是否存在于附睾腔以及ORES是否与这些结构相关而进行的研究。ORES淀粉样蛋白在小鼠附睾腔中的存在和病理的情况下，建议要么存在的机制，以中和与病理性淀粉样蛋白相关的细胞毒性或ORES是一个新的例子，一个功能性淀粉样蛋白在附睾功能的作用。
Cystatin-related epididymal spermatogenic (CRES) is the defining member of a reproductive subgroup within the family 2 cystatins of the cystatin superfamily of cysteine protease inhibitors. CRES is synthesized and secreted by the initial segment of the epididymis and is present in the sperm acrosome, suggesting roles in sperm maturation and fertilization. We have previously demonstrated that CRES is present within the epididymal lumen as monomeric (14 and N-glycosylated 19-kd forms) as well as sodium dodecyl sulfate-sensitive and sodium dodecyl sulfate-resistant high-molecular mass complexes. We have also shown that recombinant CRES protein will self-aggregate and form amyloid structures in vitro, raising the possibility that ORES might also form amyloid in vivo. Amyloid is a large protein aggregate with a specific cross-beta sheet structure, and its presence is usually associated with disease. This review discusses protein aggregation in the epididymis and provides a brief overview of amyloid formation, including recent studies in other organ systems identifying examples of amyloid that are nonpathologic and carry out biologic functions (ie, functional amyloid). Studies that were carried out to determine if amyloid is present in the epididymal lumen and if ORES is associated with these structures are also described. The presence of ORES amyloid in the mouse epididymal lumen and the absence of pathology suggest either the presence of mechanisms to neutralize the cytotoxicity associated with pathologic amyloid or that ORES is a new example of a functional amyloid with roles in epididymal function.