FBXO38 Ubiquitin Ligase Controls Sertoli Cell Maturation

0559004 - ÚMG 2023 RIV CH eng J - Článek v odborném periodiku
Dibus, Nikol - Zobalová, Eliška - Monleón, Mario Adrián Martínez - Kořínek, Vladimír - Filipp, Dominik - Petrusová, Jana - Sedláček, Radislav - Kašpárek, Petr - Čermák, Lukáš
FBXO38 Ubiquitin Ligase Controls Sertoli Cell Maturation.
Frontiers in Cell and Developmental Biology. Roč. 10, June (2022), č. článku 914053. ISSN 2296-634X. E-ISSN 2296-634X
Grant CEP: GA ČR(CZ) GA18-27408S; GA MŠMT(CZ) LM2018126
Institucionální podpora: RVO:68378050
Klíčová slova: proteasome * ubiquitin * ubiquitin ligase * spermatogenesis * sertoli cell * centromere * retinoic acid
Obor OECD: Cell biology
Impakt faktor: 5.5, rok: 2022
Způsob publikování: Open access
https://www.frontiersin.org/articles/10.3389/fcell.2022.914053/full

The ubiquitin ligase SCFFBXO38 controls centromeric chromatin by promoting the degradation of the ZXDB protein. To determine the importance of this pathway during development, Fbxo38-deficient mice were generated. The loss of FBXO38 resulted in growth retardation affecting several organs, including the male reproductive system. A detailed analysis of the mutant testes revealed pathological changes in the seminiferous tubules, accompanied by a significant decrease in sperm production and reduced fertility. In adult testes, FBXO38 was specifically expressed in Sertoli cells, a somatic population essential for spermatogenesis initiation and progression. Sertoli cells lacking FBXO38 exhibited stabilized ZXDB protein and upregulated centromeric chromatin. Furthermore, the gene expression profile revealed that the absence of FBXO38 led to a defect in Sertoli cell maturation, specifically characterized by dysregulation in genes controlling retinoic acid metabolism and intercellular communication. Consequently, we documented significant changes in their ability to initiate spermatogonial differentiation. In conclusion, we show that FBXO38 acts as a Sertoli cell maturation factor, affecting the Sertoli cell transcription program, centromere integrity, and, subsequently, the ability to control spermatogenesis.
Trvalý link: https://hdl.handle.net/11104/0332897