Sumoylation and its regulation in testicular Sertoli cells

The molecular regulation of Sertoli cells and their crosstalk with germ cells has not been fully characterized. SUMO proteins are essential for normal development and are expressed in mouse and human Sertoli cells; However, the cell-specific role of sumoylation in those cells has only started to be...

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Published in:	Biochemical and biophysical research communications Vol. 580; pp. 56 - 62
Main Authors:	Sengupta, Amitabha, Nanda, Manveet, Tariq, Shanza Baseer, Kiesel, Tania, Perlmutter, Kayla, Vigodner, Margarita
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 26-11-2021
Subjects:	Animals Apoptosis Cell Line ER stress Humans KAP1 Male Mice NOTCH signaling Proteins - metabolism Sertoli cells Sertoli Cells - cytology Sertoli Cells - metabolism SUMO ligases Sumoylation NOTCH signaling Sumoylation ER stress KAP1 Sertoli cells SUMO ligases
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Summary:	The molecular regulation of Sertoli cells and their crosstalk with germ cells has not been fully characterized. SUMO proteins are essential for normal development and are expressed in mouse and human Sertoli cells; However, the cell-specific role of sumoylation in those cells has only started to be elucidated. In other cell types, including granulosa cells, sumoylation is regulated by a SUMO ligase KAP1/Trim28. Deletion of KAP1 in Sertoli cells causes testicular degeneration; However, the role of KAP1 in those cells has not been identified. Here we show that both mouse and human Sertoli undergo apoptosis upon inhibition of sumoylation with a chemical inhibitor or via a siRNA technology. We have additionally detected changes in the Sertoli cell proteome upon the inhibition of sumoylation, and our data suggest that among others, the expression of ER/stress-related proteins is highly affected by this inhibition. Sumoylation may also regulate the NOTCH signaling which is important for the maintenance of the developing germ cells. Furthermore, we show that a siRNA-down-regulation of KAP1 in a Sertoli-derived cell line causes an almost complete inactivation of sumoylation. In conclusion, sumoylation regulates important survival and signaling pathways in Sertoli cells, and KAP1 can be a major regulator of sumoylation in these cells. •Downregulation of sumoylation causes apoptosis in mouse and human Sertoli cells•Inhibition of sumoylation activates ER stress response in primary Sertoli cells•Sumoylation regulates the level of RBPJ 1, an important NOTCH signaling regulator•KAP1 may be a major regulator of sumoylation in Sertoli cells
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authors Contributions AS, MN, SBT and KP were involved in study design, execution of the experiments, and analysis of the data. MV was involved in study design, data analysis, and manuscript writing and revision. All authors read and approved the final manuscript.
ISSN:	0006-291X 1090-2104
DOI:	10.1016/j.bbrc.2021.09.066