Involvement of calmodulin-dependent protein kinase I in the regulation of the expression of connexin 43 in MA-10 tumor Leydig cells.

Abstract

Connexin 43 (Cx43, also known as Gja1) is the most abundant testicular gap junction protein. It has a crucial role in the support of spermatogenesis by Sertoli cells in the seminiferous tubules as well as in androgen synthesis by Leydig cells. The multifunctional family of Ca2+/calmodulin-dependent protein kinases (CaMK) is composed of CaMK I, II, and IV and each can serve as a mediator of nuclear Ca2+ signals. These kinases can control gene expression by phosphorylation of key regulatory sites on transcription factors. Among these, AP-1 members cFos and cJun are interesting candidates that seem to cooperate with CaMKs to regulate Cx43 expression in Leydig cells. In this study, the Cx43 promoter region important for CaMK-dependent activation is characterized using co-transfection of plasmid reporter-constructs with different plasmids coding for CaMKs and/or AP-1 members in MA-10 Leydig cells. Here we report that the activation of Cx43 expression by cFos and cJun is increased by CaMKI. Furthermore, results from chromatin immunoprecipitation suggest that the recruitment of AP-1 family members to the proximal region of the Cx43 promoter may involve another uncharacterized AP-1 DNA regulatory element and/or protein-protein interactions with other partners. Thus, our data provide new insights into the molecular regulatory mechanisms that control mouse Cx43 transcription in testicular Leydig cells.

• Authors: Mustapha Najih, Ha Tuyen Nguyen, Luc J Martin
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 478 Issue 4 Pg. 791-805 (Apr 2023) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 36094721 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Connexin 43
• Calcium-Calmodulin-Dependent Protein Kinase Type 1
• Transcription Factor AP-1

Topics

• Male
• Mice
• Animals
• Leydig Cells (metabolism)
• Connexin 43 (genetics, metabolism)
• Calcium-Calmodulin-Dependent Protein Kinase Type 1 (metabolism)
• Transcription Factor AP-1 (genetics, metabolism)
• Neoplasms (metabolism)