Rubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function.
Autophagy degrades unnecessary proteins or damaged organelles to maintain cellular function. Therefore, autophagy has a preventive role against various diseases including hepatic disorders, neurodegenerative diseases, and cancer. Although autophagy in germ cells or Sertoli cells is known to be requi...
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Public Library of Science (PLoS)
2021
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oai:doaj.org-article:de3620c9a9d840f8b56d689a1abd05842021-12-02T20:03:24ZRubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function.1553-73901553-740410.1371/journal.pgen.1009688https://doaj.org/article/de3620c9a9d840f8b56d689a1abd05842021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009688https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Autophagy degrades unnecessary proteins or damaged organelles to maintain cellular function. Therefore, autophagy has a preventive role against various diseases including hepatic disorders, neurodegenerative diseases, and cancer. Although autophagy in germ cells or Sertoli cells is known to be required for spermatogenesis and male fertility, it remains poorly understood how autophagy participates in spermatogenesis. We found that systemic knockout mice of Rubicon, a negative regulator of autophagy, exhibited a substantial reduction in testicular weight, spermatogenesis, and male fertility, associated with upregulation of autophagy. Rubicon-null mice also had lower levels of mRNAs of Sertoli cell-related genes in testis. Importantly, Rubicon knockout in Sertoli cells, but not in germ cells, caused a defect in spermatogenesis and germline stem cell maintenance in mice, indicating a critical role of Rubicon in Sertoli cells. In mechanistic terms, genetic loss of Rubicon promoted autophagic degradation of GATA4, a transcription factor that is essential for Sertoli cell function. Furthermore, androgen antagonists caused a significant decrease in the levels of Rubicon and GATA4 in testis, accompanied by elevated autophagy. Collectively, we propose that Rubicon promotes Sertoli cell function by preventing autophagic degradation of GATA4, and that this mechanism could be regulated by androgens.Tadashi YamamuroShuhei NakamuraYu YamanoTsutomu EndoKyosuke YanagawaAyaka TokumuraTakafumi MatsumuraKiyonori KobayashiHideto MoriYusuke EnokidaniGota YoshidaHitomi ImotoTsuyoshi KawabataMaho HamasakiAkiko KumaSohei KuribayashiKentaro TakezawaYuki OkadaManabu OzawaShinichiro FukuharaTakashi ShinoharaMasahito IkawaTamotsu YoshimoriPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 8, p e1009688 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Tadashi Yamamuro Shuhei Nakamura Yu Yamano Tsutomu Endo Kyosuke Yanagawa Ayaka Tokumura Takafumi Matsumura Kiyonori Kobayashi Hideto Mori Yusuke Enokidani Gota Yoshida Hitomi Imoto Tsuyoshi Kawabata Maho Hamasaki Akiko Kuma Sohei Kuribayashi Kentaro Takezawa Yuki Okada Manabu Ozawa Shinichiro Fukuhara Takashi Shinohara Masahito Ikawa Tamotsu Yoshimori Rubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function. |
| description |
Autophagy degrades unnecessary proteins or damaged organelles to maintain cellular function. Therefore, autophagy has a preventive role against various diseases including hepatic disorders, neurodegenerative diseases, and cancer. Although autophagy in germ cells or Sertoli cells is known to be required for spermatogenesis and male fertility, it remains poorly understood how autophagy participates in spermatogenesis. We found that systemic knockout mice of Rubicon, a negative regulator of autophagy, exhibited a substantial reduction in testicular weight, spermatogenesis, and male fertility, associated with upregulation of autophagy. Rubicon-null mice also had lower levels of mRNAs of Sertoli cell-related genes in testis. Importantly, Rubicon knockout in Sertoli cells, but not in germ cells, caused a defect in spermatogenesis and germline stem cell maintenance in mice, indicating a critical role of Rubicon in Sertoli cells. In mechanistic terms, genetic loss of Rubicon promoted autophagic degradation of GATA4, a transcription factor that is essential for Sertoli cell function. Furthermore, androgen antagonists caused a significant decrease in the levels of Rubicon and GATA4 in testis, accompanied by elevated autophagy. Collectively, we propose that Rubicon promotes Sertoli cell function by preventing autophagic degradation of GATA4, and that this mechanism could be regulated by androgens. |
| format |
article |
| author |
Tadashi Yamamuro Shuhei Nakamura Yu Yamano Tsutomu Endo Kyosuke Yanagawa Ayaka Tokumura Takafumi Matsumura Kiyonori Kobayashi Hideto Mori Yusuke Enokidani Gota Yoshida Hitomi Imoto Tsuyoshi Kawabata Maho Hamasaki Akiko Kuma Sohei Kuribayashi Kentaro Takezawa Yuki Okada Manabu Ozawa Shinichiro Fukuhara Takashi Shinohara Masahito Ikawa Tamotsu Yoshimori |
| author_facet |
Tadashi Yamamuro Shuhei Nakamura Yu Yamano Tsutomu Endo Kyosuke Yanagawa Ayaka Tokumura Takafumi Matsumura Kiyonori Kobayashi Hideto Mori Yusuke Enokidani Gota Yoshida Hitomi Imoto Tsuyoshi Kawabata Maho Hamasaki Akiko Kuma Sohei Kuribayashi Kentaro Takezawa Yuki Okada Manabu Ozawa Shinichiro Fukuhara Takashi Shinohara Masahito Ikawa Tamotsu Yoshimori |
| author_sort |
Tadashi Yamamuro |
| title |
Rubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function. |
| title_short |
Rubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function. |
| title_full |
Rubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function. |
| title_fullStr |
Rubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function. |
| title_full_unstemmed |
Rubicon prevents autophagic degradation of GATA4 to promote Sertoli cell function. |
| title_sort |
rubicon prevents autophagic degradation of gata4 to promote sertoli cell function. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/de3620c9a9d840f8b56d689a1abd0584 |
| work_keys_str_mv |
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| _version_ |
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