Epididymal C4b-binding protein is processed and degraded during transit through the duct and is not essential for fertility.
Epididymal C4b-binding protein is processed and degraded during transit through the duct and is not essential for fertility.
复制标题
附子C4b结合蛋白在通过管道过渡过程中处理和降解，对于生育而言并不是必需的。
DOI：
10.1016/j.imbio.2014.11.001
复制
发表时间：
2015-04
期刊：
影响因子：
2.8
通讯作者：
Wetsel, Rick A.
中科院分区：
文献类型：
--
作者：
Nonaka, Mayumi I.;Zsigmond, Eva;Kudo, Akihiko;Kawakami, Hayato;Yoshida, Kaoru;Yoshida, Manabu;Kawano, Natsuko;Miyado, Kenji;Nonaka, Masaru;Wetsel, Rick A.
C4b结合蛋白(C4BP)是已知的循环补体调节因子之一，可防止宿主-防御补体系统的过度激活。我们已经报道，C4BP在啮齿类动物附睾中大量表达，附睾体是连接睾丸和输精管的雄性生殖器官之一，未成熟精子在通过管道的过程中获得运动和受精能力。附睾型C4BP(EpC4BP)是由上皮细胞在雄激素依赖下合成的，分泌到管腔内，并结合在经过的精子的外膜上。在本研究中，我们发现EpC4BP以一种大的寡聚体的形式分泌，类似于血清C4BP，但在附睾运输过程中被消化，并且几乎从输精管的腔液和精子表面消失。这种加工模式在血清C4BP中是未知的，提示EpC4BP和血清C4BP可能具有不同的作用机制，EpC4BP在生殖中存在新的功能。此外，EpC4BP在射精前从精子表面消失，表明EpC4BP只在附睾处起作用，不会在女性生殖道起作用，以保护精子免受补体攻击。接下来，我们建立了C4BP缺陷(C4BP−/−)小鼠，以检测EPC4BP在生殖中的可能作用。然而，C4BP−/−小鼠是可育的，C4BP−/−小鼠与野生型小鼠精子在形态、活力和自发性顶体反应速度方面没有显著差异。这些结果表明，EpC4BP参与了男性生殖，但对精子成熟不是必需的。
C4b-binding protein (C4BP) is known as one of the circulating complement regulators that prevents excessive activation of the host-defense complement system. We have reported previously that C4BP is expressed abundantly in the rodent epididymis, one of the male reproductive organs connecting the testis and vas deferens, where immature spermatozoa acquire their motility and fertilizing ability during their transit through the duct. Epididymal C4BP (EpC4BP) is synthesized androgen-dependently by the epithelial cells, secreted into the lumen, and bound to the outer membrane of the passing spermatozoa. In this study, we found that EpC4BP is secreted as a large oligomer, similar to the serum C4BP, but is digested during the epididymal transit and is almost lost from both the luminal fluid and the sperm surface in the vas deferens. Such a processing pattern is not known in serum C4BP, suggesting that EpC4BP and serum C4BP might have different functional mechanisms, and that there is a novel function of EpC4BP in reproduction. In addition, the disappearance of EpC4BP from the sperm surface prior to ejaculation suggests that EpC4BP works only in the epididymis and would not work in the female reproductive tract to protect spermatozoa from complement attack. Next, we generated C4BP-deficient (C4BP−/−) mice to examine the possible role of EpC4BP in reproduction. However, the C4BP−/− mice were fertile and no significant differences were observed between the C4BP−/− and wild-type mouse spermatozoa in terms of morphology, motility, and rate of the spontaneous acrosome reaction. These results suggest that EpC4BP is involved in male reproduction, but not essential for sperm maturation.
登录
查看更多内容
影响因子：
4.4
作者：
Holmberg, MT;Blom, AM;Meri, S
通讯作者：
Meri, S
影响因子：
4.1
作者：
CHUNG, LP;BENTLEY, DR;REID, KBM
通讯作者：
REID, KBM
影响因子：
3.6
作者：
Bray, C;Son, JH;Meizel, S
通讯作者：
Meizel, S
影响因子：
4.8
作者：
Baba, D;Kashiwabara, SI;Baba, T
通讯作者：
Baba, T
影响因子：
32.4
作者：
Brodeur, SR;Angelini, F;Geha, RS
通讯作者：
Geha, RS