A type I DnaJ homolog, DjA1, regulates androgen receptor signaling and spermatogenesis.
Two type I DnaJ homologs DjA1 (DNAJA1; dj2, HSDJ/hdj-2, 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.
Terada
Kazutoyo
K
Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. terada@gpo.kumamoto-u.ac.jp
Yomogida
Kentaro
K
Imai
Tomoaki
T
Kiyonari
Hiroshi
H
Takeda
Naoki
N
Kadomatsu
Tsuyoshi
T
Yano
Masato
M
Aizawa
Shinichi
S
Mori
Masataka
M
D022005:Adherens Junctions / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D018390:Gene Targeting; D016678:Genome; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D015741:Metribolone / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012671:Seminiferous Tubules / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013090:Spermatocytes / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000502:physiology*; D013093:Spermatogonia / Q000378:metabolism / Q000637:transplantation; D013737:Testis / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation
C494639:Dnaja1 protein, mouse; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D015741:Metribolone; D004247:DNA