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

• Published in: Cell 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
• Language: English
• 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
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-04172-y

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.