Department of Biological Sciences, Seoul National University, Seoul 151-747, Korea.
Development. 2012 Feb;139(3):568-78. doi: 10.1242/dev.075846.
Mammalian male germ cells should be maintained below body temperature for proper development. Here, we investigated how male germ cells respond to heat stress. A short exposure of mouse testes to core body temperature induced phosphorylation of eIF2α and the formation of stress granules (SGs) in male germ cells. We observed that DAZL, a germ cell-specific translational regulator, was translocated to SGs upon heat stress. Furthermore, SG assembly activity was significantly diminished in the early male germ cells of Dazl-knockout mice. The DAZL-containing SGs played a protective role against heat stress-induced apoptosis by the sequestration of specific signaling molecules, such as RACK1, and the subsequent blockage of the apoptotic MAPK pathway. Based on these results, we propose that DAZL is an essential component of the SGs, which prevent male germ cells from undergoing apoptosis upon heat stress.
哺乳动物的雄性生殖细胞应保持在体温以下以实现正常发育。在这里，我们研究了雄性生殖细胞如何应对热应激。短暂暴露于核心体温会诱导雄性生殖细胞中 eIF2α 的磷酸化和应激颗粒（SGs）的形成。我们观察到，DAZL，一种生殖细胞特异性翻译调节剂，在热应激时易位到 SGs 中。此外，在 Dazl 敲除小鼠的早期雄性生殖细胞中，SG 组装活性显著降低。DAZL 包含的 SGs 通过隔离特定的信号分子（如 RACK1）并随后阻断凋亡 MAPK 途径，对热应激诱导的细胞凋亡起到保护作用。基于这些结果，我们提出 DAZL 是 SGs 的必需组成部分，可防止雄性生殖细胞在热应激下发生凋亡。
