Nonpathological extracellular amyloid is present during normal epididymal sperm maturation.
Nonpathological extracellular amyloid is present during normal epididymal sperm maturation.
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DOI：
10.1371/journal.pone.0036394
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cornwall GA
中科院分区：
文献类型：
--
作者：
Whelly S;Johnson S;Powell J;Borchardt C;Hastert MC;Cornwall GA
淀粉样蛋白是以特异性交叉β-折叠结构为特征的聚集蛋白，并且通常与神经退行性疾病（包括阿尔茨海默病）相关。然而，最近，在正常哺乳动物组织的细胞内细胞器中发现了几种非病理性淀粉样蛋白，这表明淀粉样蛋白也可能具有生物学功能。我们以前已经表明，附睾半胱氨酸蛋白酶抑制剂克雷斯（半胱氨酸蛋白酶抑制剂相关的附睾生精），cst 8，半胱氨酸蛋白酶抑制剂超家族的生殖特异性成员，在体外形成淀粉样蛋白，这表明克雷斯淀粉样蛋白也可能在附睾腔内体内形成。在这里，我们表明含有克雷斯的淀粉样蛋白结构是正常小鼠附睾腔的组成部分，对精子没有任何明显的细胞毒性作用，并且这些结构沿着小管的长度发生变化。这些研究表明存在功能性淀粉样结构，其可能在精子成熟或维持腔环境中发挥作用，并且其本身可能沿着附睾沿着成熟变化。与以前细胞内的功能性淀粉样蛋白的例子相反，我们的研究现在表明，非病理性/功能性淀粉样蛋白也可以是细胞外的。附睾中存在细胞外和非病理性淀粉样蛋白，表明类似的淀粉样蛋白结构可能存在于其他器官系统中，并可能执行独特的组织特异性功能。
Amyloids are aggregated proteins characterized by a specific cross-β-sheet structure and are typically associated with neurodegenerative diseases including Alzheimer's disease. Recently, however, several nonpathological amyloids have been found in intracellular organelles of normal mammalian tissues suggesting that amyloid may also carry out biological functions. We previously have shown that the epididymal cystatin CRES (cystatin-related epididymal spermatogenic), cst8, a reproductive-specific member of the cystatin superfamily of cysteine protease inhibitors, forms amyloid in vitro suggesting that CRES amyloid may also form in vivo within the epididymal lumen. Here we show that amyloid structures containing CRES are a component of the normal mouse epididymal lumen without any apparent cytotoxic effects on spermatozoa and that these structures change along the length of the tubule. These studies suggest the presence of a functional amyloid structure that may carry out roles in sperm maturation or maintenance of the luminal milieu and which itself may undergo maturational changes along the epididymis. In contrast to previous examples of functional amyloid which were intracellular, our studies now show that nonpathological/functional amyloid can also be extracellular. The presence of an extracellular and nonpathological amyloid in the epididymis suggests that similar amyloid structures may be present in other organ systems and may carry out distinctive tissue-specific functions.
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DOI：
10.1126/science.1173155
发表时间：
2009-07-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Maji SK;Perrin MH;Sawaya MR;Jessberger S;Vadodaria K;Rissman RA;Singru PS;Nilsson KP;Simon R;Schubert D;Eisenberg D;Rivier J;Sawchenko P;Vale W;Riek R
通讯作者：
Riek R
影响因子：
15.1
作者：
Kayed R;Head E;Sarsoza F;Saing T;Cotman CW;Necula M;Margol L;Wu J;Breydo L;Thompson JL;Rasool S;Gurlo T;Butler P;Glabe CG
通讯作者：
Glabe CG
影响因子：
9.8
作者：
Fowler DM;Koulov AV;Alory-Jost C;Marks MS;Balch WE;Kelly JW
通讯作者：
Kelly JW
影响因子：
2.5
作者：
CORNWALL, GA;HANN, SR
通讯作者：
HANN, SR
影响因子：
2.9
作者：
Turner, Terry T.;Johnston, Daniel S.;Finger, Joshua N.
通讯作者：
Finger, Joshua N.