A type I DnaJ homolog, DjA1, regulates androgen receptor signaling and spermatogenesis
A type I DnaJ homolog, DjA1, regulates androgen receptor signaling and spermatogenesis
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DOI：
10.1038/sj.emboj.7600549
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发表时间：
2005-02-09
期刊：
影响因子：
11.4
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Terada, K;Yomogida, K;Mori, M
两种 I 型 DnaJ 同源物 DjA1 (DNAJA1; dj2, HSDJ/hdj2, rdj1) 和 DjA2 (DNAJA2; dj3, rdj2) 在体外蛋白质折叠和线粒体蛋白质输入中与 Hsp70 的共伴侣类似。为了研究 DjA1 的体内作用，我们培育了 DjA1 突变小鼠。令人惊讶的是，小鼠 DjA1 的缺失导致精子发生的严重缺陷，其中涉及异常的雄激素信号传导。将绿色荧光蛋白标记的精原细胞移植到 DjA1(-/-) 小鼠体内的实验揭示了支持细胞在第 8 步和第 9 步维持精子发生方面的主要缺陷。在 DjA1(-/-) 小鼠的支持细胞中，雄激素受体明显积累，并且几个雄激素反应基因（包括 Pem 和 testin）的转录增强。 DjA1(-/-) 小鼠中支持细胞-生殖细胞粘附连接的破坏也很明显。 DjA1(-/-) 成纤维细胞和原代支持细胞的实验表明雄激素受体信号传导异常。这些结果揭示了 DjA1 在精子发生中的关键作用，并表明 DjA1 和 DjA2 在体内功能并不相同。
Two type I DnaJ homologs DjA1 (DNAJA1; dj2, HSDJ/hdj2, rdj1) and DjA2 (DNAJA2; dj3, rdj2) work similarly as a cochaperone of Hsp70s in protein folding and mitochondrial protein import in vitro. To study the in vivo role of DjA1, we generated DjA1-mutant mice. Surprisingly, loss of DjA1 in mice led to severe defects in spermatogenesis that involve aberrant androgen signaling. Transplantation experiments with green fluorescent protein-labeled spermatogonia into DjA1(-/-) mice revealed a primary defect of Sertoli cells in maintaining spermiogenesis at steps 8 and 9. In Sertoli cells of DjA1(-/-) mice, the androgen receptor markedly accumulated with enhanced transcription of several androgen-responsive genes, including Pem and testin. Disruption of Sertoli - germ cell adherens junctions was also evident in DjA1(-/-) mice. Experiments with DjA1(-/-) fibroblasts and primary Sertoli cells indicated aberrant androgen receptor signaling. These results revealed a critical role of DjA1 in spermiogenesis and suggest that DjA1 and DjA2 are not functionally equivalent in vivo.