Specific deletion of protein phosphatase 6 catalytic subunit in Sertoli cells leads to disruption of spermatogenesis

Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In...

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Published inCell death & disease Vol. 12; no. 10; pp. 883 - 13
Main Authors Lei, Wen-Long, Li, Yuan-Yuan, Meng, Tie-Gang, Ning, Yan, Sun, Si-Min, Zhang, Chun-Hui, Gui, Yaoting, Wang, Zhen-Bo, Qian, Wei-Ping, Sun, Qing-Yuan
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 27.09.2021
Springer Nature B.V
Nature Publishing Group
Subjects
13/1
13/2
13/31
13/51
14/1
631/136/2434/1822
64/110
64/60
692/699/2732/1577
82/58
82/80
Adherens junctions
Animals
Antibodies
Apoptosis
beta Catenin - metabolism
Biochemistry
Bioinformatics
Biomedical and Life Sciences
Catalytic Domain
Cell Biology
Cell Culture
Cell differentiation
Cell interactions
Cell survival
Epididymis - metabolism
Epithelium
Exons - genetics
Gene Deletion
Germ cells
Immunology
Infertility, Male - genetics
Integrases - metabolism
Life Sciences
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutants
Phosphatase
Phosphoprotein Phosphatases - deficiency
Phosphoprotein Phosphatases - metabolism
Phosphoproteins - metabolism
Phosphorylation
Protein phosphatase
Proteome - metabolism
Sertoli cells
Sertoli Cells - metabolism
Spermatogenesis
Spermatozoa - metabolism
Testis - metabolism
Testis - pathology
β-Catenin
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Abstract Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6c F/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of β-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal β-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating β-catenin at S552.
AbstractList Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6cF/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of β-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal β-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating β-catenin at S552.
Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6c mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of β-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal β-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating β-catenin at S552.
Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6c F/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of β-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal β-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating β-catenin at S552.
Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6cF/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of β-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal β-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating β-catenin at S552.Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6cF/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of β-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal β-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating β-catenin at S552.
Abstract Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6c F/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of β-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal β-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating β-catenin at S552.
ArticleNumber 883
Author Sun, Si-Min
Gui, Yaoting
Li, Yuan-Yuan
Meng, Tie-Gang
Sun, Qing-Yuan
Zhang, Chun-Hui
Wang, Zhen-Bo
Lei, Wen-Long
Qian, Wei-Ping
Ning, Yan
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Snippet Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that...
Abstract Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We...
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Adherens junctions
Animals
Antibodies
Apoptosis
beta Catenin - metabolism
Biochemistry
Bioinformatics
Biomedical and Life Sciences
Catalytic Domain
Cell Biology
Cell Culture
Cell differentiation
Cell interactions
Cell survival
Epididymis - metabolism
Epithelium
Exons - genetics
Gene Deletion
Germ cells
Immunology
Infertility, Male - genetics
Integrases - metabolism
Life Sciences
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutants
Phosphatase
Phosphoprotein Phosphatases - deficiency
Phosphoprotein Phosphatases - metabolism
Phosphoproteins - metabolism
Phosphorylation
Protein phosphatase
Proteome - metabolism
Sertoli cells
Sertoli Cells - metabolism
Spermatogenesis
Spermatozoa - metabolism
Testis - metabolism
Testis - pathology
β-Catenin
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Title Specific deletion of protein phosphatase 6 catalytic subunit in Sertoli cells leads to disruption of spermatogenesis
URI https://link.springer.com/article/10.1038/s41419-021-04172-y
https://www.ncbi.nlm.nih.gov/pubmed/34580275
https://www.proquest.com/docview/2576737074
https://www.proquest.com/docview/2577458358
https://pubmed.ncbi.nlm.nih.gov/PMC8476514
https://doaj.org/article/e69ee08b6a31435383c03a94f2952371
Volume 12
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