Sertoli cell vacuolization and abnormal germ cell adhesion in mice deficient in an inositol polyphosphate 5-phosphatase

Sertoli cell vacuolization and abnormal germ cell adhesion in mice deficient in an inositol polyphosphate 5-phosphatase
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DOI:
10.1095/biolreprod66.5.1522
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发表时间:
2002-05-01
影响因子:
3.6
通讯作者:
Nussbaum, RL
Nussbaum, RL
中科院分区:
生物学2区
文献类型:
--
作者:
Hellsten, E;Bernard, DJ;Nussbaum, RL

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生殖细胞分化过程中细胞相互作用的动态性质及其从基膜到曲细精管管腔的移位需要睾丸中存在复杂且调节良好的细胞粘附机制。发育中的生殖细胞的成功迁移的特征在于生殖细胞和支持细胞(支持和滋养发育中的配子的睾丸的极化体细胞)之间的含钙粘蛋白的粘附连接的动态断裂和重组。在这里,我们证明了异常肿胀,肌动蛋白涂层,内体样结构,包含完整的粘附连接和染色阳性的N-钙粘蛋白和β-连环蛋白在支持细胞胞质溶胶的小鼠缺乏Inpp 5 b,肌醇多磷酸5-磷酸酶的积累。在这些异常结构形成的同时,发育中的生殖细胞过早地从生精上皮释放并脱落到附睾中。我们的研究结果表明,lnpp 5 b在调节睾丸细胞粘附和与邻近细胞形成连接复合物中的作用,并强调了磷酸肌醇在精子发生中的重要和必不可少的作用。
The dynamic nature of cellular interactions during differentiation of germ cells and their translocation from the basement membrane to the lumen of the seminiferous tubules requires the existence of complex and well-regulated cellular adhesion mechanisms in the testis. Successful migration of the developing germ cells is characterized by dynamic breakage and reformation of cadherin-containing adherens junctions between the germ cells and Sertoli cells, the polarized somatic cells of the testis that support and nourish the developing gametes. Here, we demonstrate the accumulation of abnormally swollen, actin-coated, endosome-like structures that contain intact adherens junctions and stain positive for N-cadherin and beta-catenin in the Sertoli cell cytosol of mice deficient in Inpp5b, an inositol polyphosphate 5-phosphatase. Simultaneous to the formation of these abnormal structures, developing germ cells are prematurely released from the seminiferous epithelium and sloughed into the epididymis. Our results demonstrate a role for lnpp5b in the regulation of cell adhesion in the testis and in the formation of junctional complexes with neighboring cells, and they emphasize the important and essential role of phosphoinositides in spermatogenesis.