Maekawa Mamiko, Toyama Yoshiro, Yasuda Masahiro, Yagi Takeshi, Yuasa Shigeki
Department of Anatomy and Developmental Biology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Biol Reprod. 2002 Jan;66(1):211-21. doi: 10.1095/biolreprod66.1.211.
Fyn is a member of the Src family of non-receptor-type tyrosine kinases and plays an important role in signal transductions regulating cell proliferation and differentiation. Fyn immunoreactivity was localized in the Sertoli cells of mouse testes. Although fyn-deficient adult male mice were fertile, a significant reduction in testis weight and degenerated germ cells were observed at 3 and 4 wk of age. Electron microscopic examination revealed that fyn -/- testis has ultrastructural abnormalities in the specialized junctional structures of the Sertoli cells, the ectoplasmic specializations. Unusual vesicular structures were found in the actin filament layers of the ectoplasmic specializations of mutant mice. Immunohistochemical studies demonstrated that both Fyn and actin filaments were concentrated in the areas of ectoplasmic specializations. At these sites, a high level of phosphotyrosine was also immunostained in wild-type testes, whereas phosphotyrosine immunoreactivity was reduced in fyn -/- testes. Immunoblot analyses revealed that Fyn was mainly distributed within the Triton X-100-insoluble cytoskeletal fraction prepared from wild-type testes, suggesting that Fyn might be associated with cytoskeletal proteins such as actin filaments. These findings suggest that Fyn kinase functions at the ectoplasmic specializations of the Sertoli cells in the testes, regulating the dynamics of cytoskeletal proteins. Fyn-mediated signal transduction in the Sertoli cells may affect the survival and differentiation of germ cells at a specific stage during spermatogenesis.
Fyn是非受体型酪氨酸激酶Src家族的成员,在调节细胞增殖和分化的信号转导中起重要作用。Fyn免疫反应性定位于小鼠睾丸的支持细胞中。虽然fyn基因缺失的成年雄性小鼠具有生育能力,但在3周龄和4周龄时观察到睾丸重量显著减轻以及生殖细胞退化。电子显微镜检查显示,fyn基因敲除小鼠的睾丸在支持细胞的特殊连接结构即外质特化结构中存在超微结构异常。在突变小鼠外质特化结构的肌动蛋白丝层中发现了异常的囊泡结构。免疫组织化学研究表明,Fyn和肌动蛋白丝都集中在外质特化区域。在这些部位,野生型睾丸中也有高水平的磷酸酪氨酸免疫染色,而在fyn基因敲除小鼠的睾丸中磷酸酪氨酸免疫反应性降低。免疫印迹分析显示,Fyn主要分布在从野生型睾丸制备的不溶于Triton X-100的细胞骨架组分中,这表明Fyn可能与肌动蛋白丝等细胞骨架蛋白相关。这些发现表明,Fyn激酶在睾丸支持细胞的外质特化结构中发挥作用,调节细胞骨架蛋白的动态变化。支持细胞中Fyn介导的信号转导可能在精子发生的特定阶段影响生殖细胞的存活和分化。