Role of cell adhesion molecule nectin-3 in spermatid development

Role of cell adhesion molecule nectin-3 in spermatid development
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DOI:
10.1111/j.1365-2443.2006.01006.x
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发表时间:
2006-09-01
期刊:
影响因子:
2.1
通讯作者:
Takai, Yoshimi
Takai, Yoshimi
中科院分区:
生物学4区
文献类型:
--
作者:
Inagaki, Maiko;Irie, Kenji;Takai, Yoshimi

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睾丸生精上皮含有两种细胞间连接:支持-支持连接和支持-精子细胞连接。前者具有紧固性和粘附性,后者没有。钙非依赖性免疫球蛋白样细胞-细胞黏附分子Nectin-2和Nectin-3分别不对称地定位于Sertoli细胞侧和Sertoli-精子细胞连接的精细胞侧。它们通过异嗜性的反式相互作用在两个细胞之间建立联系。Nectin-2(-/-)小鼠表现出男性特有的不育,支持-精子细胞连接中断,精子细胞发育形态受损。在这里,我们报告了Nectin-3(-/-)小鼠的睾丸表型,这些小鼠表现出男性特有的不育。Nectin-3(-/-)小鼠在精子形态发生的后期阶段存在缺陷,包括细胞核扭曲和线粒体分布异常,以及Nectin-2在支持-精子细胞连接处的定位缺陷。将野生型生精干细胞移植到Nectin-3(-/-)睾丸中,部分挽救了精子形态发生的这些缺陷。这些结果表明,Nectin-2和Nectin-3之间的异嗜性反式相互作用对于Sertoli-精子细胞连接的形成和维持是必不可少的,支持-精子细胞连接在精子细胞的发育中起着关键作用。
Seminiferous epithelia of the testes contain two types of intercellular junctions: Sertoli-Sertoli junctions and Sertoli-spermatid junctions. The former junctions are equipped with tight and adherens junctions while the latter junctions are not. Ca2+-independent immunoglobulin-like cell-cell adhesion molecules, nectin-2 and nectin-3, asymmetrically localize at the Sertoli cell side and at the spermatid side of Sertoli-spermatid junctions, respectively. They heterophilically trans-interact to make contact between the two cells. Nectin-2(-/-) mice have shown male-specific infertility, disrupted Sertoli-spermatid junctions and morphologically impaired spermatid development. Here we report testicular phenotypes of nectin-3(-/-) mice exhibiting male-specific infertility. Nectin-3(-/-) mice had defects in the later steps of sperm morphogenesis including distorted nuclei and abnormal distribution of mitochondria, as well as in localization of nectin-2 at the Sertoli-spermatid junctions. Transplantation of wild-type spermatogenic stem cells into the nectin-3(-/-) testes partially rescued these defects in sperm morphogenesis. These results indicate that the heterophilic trans interaction between nectin-2 and nectin-3 is essential for the formation and maintenance of Sertoli-spermatid junctions that plays a critical role in spermatid development.