DAZL is essential for stress granule formation implicated in germ cell survival upon heat stress

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 eIF2 alpha 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.