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

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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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

Current work was funded by the New Brunswick Innovation Foundation (NBIF) (#RAI-2018-063 to L.J.M.) and the Natural Sciences and Engineering Research Council (NSERC) of Canada (#386557 to L.J.M).

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  1. Biology Department, Université de Moncton, 18, avenue Antonine Maillet, Moncton, NB, E1A 3E9, Canada

    Mustapha Najih, Ha Tuyen Nguyen & Luc J. Martin

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MN and LJM contributed to the experimental design. MN and HTN performed the experiments and statistical analyses. MN wrote the first draft of the manuscript. LJM and HTN revised the manuscript. All authors read and approved the final manuscript.

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Najih, M., Nguyen, H.T. & Martin, L.J. Involvement of calmodulin-dependent protein kinase I in the regulation of the expression of connexin 43 in MA-10 tumor Leydig cells. Mol Cell Biochem 478, 791–805 (2023). https://doi.org/10.1007/s11010-022-04553-7

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