Joint research with Yonsei University-GILO Foundation discovered the role of microtubule-associated serine/threonine kinase family member 4

 

A Korean research team has identified the mechanism of action of the protein that regulates spermatogonial stem cells which is essential in treating male infertility, suggesting the potential therapeutic options for male infertility.

 

MedPacto (CEO Seong-jin Kim), a genome-based drug discovery and a clinical-stage biotechnology company, and its joint research team, Yonsei University (Professor Hansung Jeong) and GILO Foundation have announced that they have discovered MAST4 protein which is proven to be essential to cell cycle maintenance and self-renewal regulation of spermatogonial stem cells on the Feb 1st.

 

The study was published in the international academic journal 'Cell proliferation (IF: 8.755)'.

 

Spermatogenesis is a complex and cyclic process involving spermatogonial stem cell(SSC) differentiation, meiotic cell division, and sperm production. SSCs continuously maintain spermatogenesis via self-renewal to replenish themselves and differentiation that generates sperm. However, when the MAST4 protein in Sertoli cells is deficient, the self-renewal of SSCs decreases resulting in Sertoli cell-only syndrome, which causes male infertility.

 

This newly identified study result, discovering the specific interaction between Sertoli cells which plays a pivotal role in spermatogenesis and SSCs, could lead to the development of new treatments for male infertility.

 

The research team discovered that the expression of PLZF(Promyelocytic leukemia zinc finger), known to regulate SSCs cycle status, was significantly decreased in the testes of MAST4 knock-out mice showing a loss of maintenance of SSC self-renewal as the cell cycle in SSCs had been extended.

 

It is identified that MAST4 phosphorylates and activates PLZF protein by inducing CDK2(Cyclin-dependant kinase2) resulting in the regulations of SSC self-renewal-related genes.

 

The research team also confirmed the increase of CDK2-PLZF interaction when the CXCL12 (C-X-C Motif Chemokine Ligand 12) protein secreted from Sertoli cells in the MAST4 pathway is activated. This suggests that Sertoli cell signaling leading to FGF2-MAST4-CXCL12 regulates the self-renewal of SSCs by promoting CDK2-PLZF interaction and activation in SSCs.

 

The research team had previously confirmed the exhibition of Sertoli cell-only syndrome in the MAST4 knock-out mice and identified the correlation between the ERM transcription factor and MAST4 protein that involves in the regulation of self-renewal of SSCs in Sertoli cells.

 

"We have newly identified the specific mechanism of MAST4 protein that regulates SSCs which is critical in the treatment of male infertility, from a vantage point of cell cycle regulation. We found that the FGF2-MAST4-CXCL12 pathway of Sertoli cells and SSCs regulates self-renewal of SSCs.” stated the representative of the research team.