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PMID:15660130
| Citation |
Terada, K, Yomogida, K, Imai, T, Kiyonari, H, Takeda, N, Kadomatsu, T, Yano, M, Aizawa, S and Mori, M (2005) A type I DnaJ homolog, DjA1, regulates androgen receptor signaling and spermatogenesis. EMBO J. 24:611-22 |
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| Abstract |
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. |
| Links |
PubMed PMC548655 Online version:10.1038/sj.emboj.7600549 |
| Keywords |
Adherens Junctions/metabolism; Adherens Junctions/pathology; Animals; Apoptosis; Base Sequence; DNA/genetics; Female; Gene Targeting; Genome; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; HSP40 Heat-Shock Proteins; Heat-Shock Proteins/deficiency; Heat-Shock Proteins/genetics; Heat-Shock Proteins/physiology; Male; Metribolone/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Phenotype; Receptors, Androgen/genetics; Receptors, Androgen/metabolism; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Seminiferous Tubules/metabolism; Seminiferous Tubules/pathology; Signal Transduction; Spermatocytes/metabolism; Spermatocytes/pathology; Spermatogenesis/physiology; Spermatogonia/metabolism; Spermatogonia/transplantation; Testis/metabolism; Testis/pathology; Transcriptional Activation |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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