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 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.
Department of Biological Sciences, Seoul National University, Seoul 151-747, Korea.
Byunghyuk
B
Kim
Howard J
HJ
Cooke
Kunsoo
K
Rhee
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D003594:Cytoplasmic Granules / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D018869:Heat-Shock Response; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
C508515:DAZL protein, mouse; D015852:Eukaryotic Initiation Factor-2; D009479:Neuropeptides; C090294:RACK1 protein, mouse; D016601:RNA-Binding Proteins; D000075370:Receptors for Activated C Kinase