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Extracellular quality control in the epididymis

Asian Journal of Andrology 2007年第4期9卷 500-507页

作者： gail A. cornwall H. Henning von Horsten Douglas Swartz Seethal Johnson Kim Chau Sandra Whelly Department of Cell Biology and Biochemistry Texas Tech University Health Sciences Center Lubbock TX 79430 USA

The epididymal lumen represents a unique extracellular environment because of the active sperm maturation process that takes place within its confines. Although much focus has been placed on the interaction of epididymal secretory proteins with spermatozoa in the lumen, very little is known regarding how the complex epididymal milieu as a whole is maintained, including mechanisms to prevent or control proteins that may not stay in their native folded state following secretion. Because some misfolded proteins can form cytotoxic aggregate structures known as amyloid, it is likely that control/surveillance mechanisms exist within the epididymis to protect against this process and allow sperm maturation to occur. To study protein aggregation and to identify extracellular quality control mechanisms in the epididymis, we used the cystatin family of cysteine protease inhibitors, including cystatin-related epididymal spermatogenic and cystatin C as molecular models because both proteins have inherent properties to aggregate and form amyloid. In this chapter, we present a brief summary of protein aggregation by the amyloid pathway based on what is known from other organ systems and describe quality control mechanisms that exist intracellularly to control protein misfolding and aggregation. We then present a summary of our studies of cystatinrelated epididymal spermatogenic （CRES） oligomerization within the epididymal lumen, including studies suggesting that transglutaminase cross-linking may be one mechanism of extracellular quality control within the epididymis. （Asian J Androl 2007 July; 9： 500-507）

关键词： epididymis protein aggregation extracellular quality control cystatin transglutaminase

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胱蛋白酶抑制剂相关的附睾精子发生基因的调节和功能

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中华男科学杂志 2002年第5期8卷 313-318页

作者： gail a cornwall Nelson HSIA DepartmentofCellBiologyandBiochemistry DepartmentofCellBiologyandBiochemistry TexasTechUniversityHealthSciencesCenterLubbockTX79430USATexasTechUniversityHealthSciencesCenterLubbockTX79430USA

CRES(cystatin relatedepididymalspermatogenic,胱蛋白酶抑制剂相关的附睾精子发生 )蛋白是胱蛋白酶抑制剂(cystatin)超家族中家族 2的一个亚类。然而 ,与cystatinC的广泛性表达不同 ,Cres基因只在分裂后的生殖细胞、附睾头部近端和腺... 详细信息

CRES(cystatin relatedepididymalspermatogenic,胱蛋白酶抑制剂相关的附睾精子发生 )蛋白是胱蛋白酶抑制剂(cystatin)超家族中家族 2的一个亚类。然而 ,与cystatinC的广泛性表达不同 ,Cres基因只在分裂后的生殖细胞、附睾头部近端和腺垂体促性腺激素细胞中表达。cystatin对C1半胱氨酸蛋白酶抑制作用的发挥必须有 3个共有位点的参与 ,而CRES蛋白缺少其中的 2个位点。因此 ,CERS在生殖系统和神经内分泌系统中的功能也许是独特的和组织特异性的。本文概述了以下方面的研究 :①Cres基因启动子及其转录调节蛋白相关的可能对Cres的组织特异性表达有重要作用的DNA结合位点。②CRES蛋白的生物学功能。Norethern印迹法、凝胶转移分析和瞬时转染实验均表明 ,附睾和促性腺激素细胞中主要表达C EBP家族中的C EBPβ(CCAAT 增强子结合蛋白 ) ,且C EBPβ对于Cres基因在这两个组织中的高表达是必不可少的。另外 ,构建了表达氯霉素乙酰基转移酶 (CAT)报告基因的转基因小鼠 ,CAT报告基因由Cres基因 5′端 1 6kb的启动子所调控。分析显示 ,CATmRNA仅在生殖细胞中表达 ,说明Cres 5′端 1 6kb的侧翼区含有调控CAT在睾丸中表达的DNA序列 ,而缺乏指导CAT在附睾中表达的序列 ,或者此1 6kb的DNA片段存在Cres的负调节成分。最后 ,

关键词：胱蛋白酶抑制剂附睾精子发生基因调控

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Age-dependent expression of the cystatin-related epididymal spermatogenic （Cres） gene in mouse testis and epididymis

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Asian Journal of Andrology 2007年第3期9卷 305-311页

作者： Qing Yuan Qiang-Su Guo gail A. cornwall Chen Xu Yi-Fei Wang Department of Histology ＆ Embryology Shanghai Jiaotong University School of Medicine Shanghai 200025 China Departments of Cell Biology and Biochemistry Texas Technology University Health Science Center Lubbock TX USA

Aim： To investigate the spatial and temporal expression of the cystatin-related epididymal spermatogenic （Cres） gene in mouse testis and epididymis during postnatal development. Methods： The QuantiGene assay and indirect immunofluorescence technique were used to examine the Cres mRNA and Cres protein level in mouse testis and epididymis on postnatal days 14, 20, 22, 28, 35, 49, 70 and 420. Results：（1） In both the testis and epididymis, Cres mRNA was fast detected on day 20, then it increased gradually from day 20 to day 70, and the high expression level maintained till day 420. （2） In the testis, the Cres protein was exclusively localized to the elongating spermatids and was first detected on day 22. The number of Cres-positive spermatids increased progressively till day 49. From day 49 to day 420, the number of Cres-positive cells was almost stable. （3） The Cres protein was first detected on day 20 in the proximal caput epididymal epithelium. By day 35, the expression level of the Cres protein increased dramatically and the high level was maintained till day 420. Moreover, the luminal fluid of the midcaput epididymis was also stained Cres-positive from day 35 on. No Cres-positive staining was observed in distal caput, corpus and cauda epididymis throughout. Conclusion： The Cres gene displays a specific age-dependent expression pattern in mouse testis and epididymis on both the mRNA and protein level.

关键词： cystatin-related epididymal spermatogenic gene spermatogenesis sperm maturation development

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