Members of the AP-1 Family of Transcription Factors Regulate the Expression of Gja1 in Mouse GC-1 Spermatogonial Cells

Mustapha Najih,Luc J Martin,Mariama Diawara,Ha Tuyen Nguyen,Audrey Basque

doi:10.3390/app12031408

Mustapha Najih, Luc J Martin + Show 3 more

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https://doi.org/10.3390/app12031408

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Journal: Applied sciences	Publication Date: Jan 28, 2022
Citations: 3	License type: CC BY 4.0

Affiliation: Université de Moncton

Abstract

Gap junctions, mainly formed by Gja1 (Connexin43), play an essential role in the regulation of proliferation and differentiation of spermatogonia in the testis. Regulation of the abundance of Gja1 in spermatogonia involves various processes, including gene transcription, mRNA maturation, protein synthesis, post-translational modifications, plasma membrane integration and protein degradation. However, gene expression of Gja1 is abnormally decreased in most testicular germ cell tumors. Hence, a better understanding of the mechanisms of transcriptional regulation of Gja1 in spermatogonia is essential to understand how the loss of its expression occurs during the development of testicular cancer. As in other cell types, activator protein-1 (AP-1) transcription factors may be involved in such regulatory process. Thus, AP-1 members were overexpressed in GC-1 cells to assess their impact on Gja1 expression. We showed that Jun and Fosl2 cooperate to activate the Gja1 promoter in GC-1 cells. Furthermore, the recruitment of Jun to the proximal region (−153 to +46 bp) of the Gja1 promoter has been confirmed via chromatin immunoprecipitation. Protein kinase A and calcium-calmodulin protein kinase I also contribute to the activation of Gja1 expression by improving the cooperation between AP-1 factors. Therefore, the reduction in Gja1 expression in testicular germ cell tumors may involve a loss of cooperation between AP-1 factors.

Highlights

In the seminiferous tubules of the testis, spermatogonia differentiate into spermatocytes and spermatids during spermatogenesis, leading to the formation of spermatozoa
Based on previously published RNA-Seq data (SRA: PRJNA523810 and PRJNA491649) [21,26], expression levels for different connexins, activator protein-1 (AP-1) family members and calmodulin-dependent protein kinases (CaMK) are presented in spermatogonial stem cells, spermatogonia, spermatocytes and GC-1 cells (Figure 1)
Among transcription factors potentially involved in the regulation of Gja1 expression, AP-1 family members Jun, Junb, Fos and Fosl2 are highly expressed in spermatogonia (Figure 1C), whereas Jun, Junb, Jund and Fosl2 are predominantly expressed in GC-1 cells (Figure 1D)

Summary

Introduction

In the seminiferous tubules of the testis, spermatogonia differentiate into spermatocytes and spermatids during spermatogenesis, leading to the formation of spermatozoa. Spermatogonia are intimately associated with the supporting Sertoli cells. The communication between these cells involves the formation of gap junctions, of which Gja. Each cell participating in the formation of a gap junction harbors a connexon, made of six connexin protein units, on its plasma membrane. The gap junction is made by the interaction between two connexons from adjacent cells and allows the exchange of different second messengers and small molecules (

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