Long Glucocorticoid-induced Leucine Zipper (L-GILZ) Protein Interacts with Ras Protein Pathway and Contributes to Spermatogenesis Control
Long Glucocorticoid-induced Leucine Zipper (L-GILZ) Protein Interacts with Ras Protein Pathway and Contributes to Spermatogenesis Control
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DOI：
10.1074/jbc.m111.316372
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发表时间：
2012-01-06
影响因子：
4.8
通讯作者：
Riccardi, Carlo
中科院分区：
文献类型：
--
作者：
Bruscoli, Stefano;Velardi, Enrico;Riccardi, Carlo
精原细胞的正确功能对于维持整个生命过程中的精子发生至关重要，但调节未分化精原细胞增殖、分化和存活的细胞途径仅部分已知。我们发现长的糖皮质激素诱导的亮氨酸拉链（L-GILZ）在精原细胞和初级精母细胞中高度表达，并控制精子发生。基因敲除小鼠中的Gilz缺陷（Gilz KO）导致精子发生的第一个周期内生殖细胞谱系的完全丧失，导致雄性不育。精子发生失败是生殖细胞固有的，与未分化精原细胞的增殖增加和异常分化以及Ras信号通路的过度活跃相关，如ERK和Akt磷酸化的增加所示。精原细胞的分化不能超过第一次减数分裂的前期，这是由于大量的细胞凋亡与未修复的染色体损伤的积累有关。这些结果表明，L-GILZ作为一个新的重要因素未分化精原细胞功能和精子发生。
Correct function of spermatogonia is critical for the maintenance of spermatogenesis throughout life, but the cellular pathways regulating undifferentiated spermatogonia proliferation, differentiation, and survival are only partially known. We show here that long glucocorticoid-induced leucine zipper (L-GILZ) is highly expressed in spermatogonia and primary spermato-cytes and controls spermatogenesis. Gilz deficiency in knockout (gilz KO) mice leads to a complete loss of germ cell lineage within first cycles of spermatogenesis, resulting in male sterility. Spermatogenesis failure is intrinsic to germ cells and is associated with increased proliferation and aberrant differentiation of undifferentiated spermatogonia and with hyperactivity of Ras signaling pathway as indicated by an increase of ERK and Akt phosphorylation. Spermatogonia differentiation does not proceed beyond the prophase of the first meiotic division due to massive apoptosis associated with accumulation of unrepaired chromosomal damage. These results identify L-GILZ as a novel important factor for undifferentiated spermatogonia function and spermatogenesis.