Possible function of the ADAM1a/ADAM2 fertilin complex in the appearance of ADAM3 on the sperm surface

Possible function of the ADAM1a/ADAM2 fertilin complex in the appearance of ADAM3 on the sperm surface
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DOI:
10.1074/jbc.m314249200
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发表时间:
2004-08-13
影响因子:
4.8
通讯作者:
Baba, T
Baba, T
中科院分区:
生物学2区
文献类型:
--
作者:
Nishimura, H;Kim, E;Baba, T

文献摘要

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在小鼠中,在睾丸中产生两种不同的ADAM 1(受精素α)亚型,ADAM 1a和ADAM 1b。ADAM 1a位于睾丸生殖细胞的内质网内,而附睾精子仅在质膜上含有ADAM 1b。在这项研究中,我们表明,ADAM 1a的损失导致男性不育,因为精子从子宫通过子宫输卵管连接处迁移到输卵管的能力严重受损。然而,ADAM 1a缺陷小鼠的附睾精子能够在体外形成卵丘完整、透明卵完整的卵子,尽管卵丘细胞分散延迟,与透明卵的粘附/结合减少。在检测的睾丸(精子)特异性蛋白质中,只有ADAM 3(cyritestin)的水平在ADAM 1a缺陷小鼠精子中强烈降低。此外,精子表面上的ADAM 3的出现依赖于ADAM 1a和ADAM 2之间的受精素蛋白复合物的形成(fertilin beta)在睾丸生殖细胞中,虽然没有发现受精素复合物与ADAM 3之间的直接相互作用。这些结果表明,ADAM 1a/ADAM 2受精蛋白可能参与特异性精子蛋白包括ADAM 3从睾丸生殖细胞内质网到精子的选择性转运。细胞表面。然后这些蛋白质可以参与精子迁移到输卵管,卵丘细胞的扩散,以及精子与透明质膜的结合。
In mouse, two different isoforms of ADAM1 (fertilin alpha), ADAM1a and ADAM1b, are produced in the testis. ADAM1a is localized within the endoplasmic reticulum of testicular germ cells, whereas epididymal sperm contain only ADAM1b on the plasma membrane. In this study, we show that the loss of ADAM1a results in the male infertility because of the severely impaired ability of sperm to migrate from the uterus into the oviduct through the uterotubal junction. However, epididymal sperm of ADAM1a-deficient mice were capable of fertilizing cumulus-intact, zona pellucida-intact eggs in vitro despite the delayed dispersal of cumulus cells and the reduced adhesion/binding to the zona pellucida. Among testis (sperm)-specific proteins examined, only the level of ADAM3 (cyritestin) was strongly reduced in ADAM1a-deficient mouse sperm. Moreover, the appearance of ADAM3 on the sperm surface was dependent on the formation of a fertilin protein complex between ADAM1a and ADAM2 (fertilin beta) in testicular germ cells, although no direct interaction between the fertilin complex and ADAM3 was found. These results suggest that ADAM1a/ADAM2 fertilin may be implicated in the selective transport of specific sperm proteins including ADAM3 from the endoplasmic reticulum of testicular germ cells onto the cell surface. These proteins then can participate in sperm migration into the oviduct, the dispersal of cumulus cells, and sperm binding to the zona pellucida.