Phosphorylation and expression level of nucleophosmin is regulated by SUMOylation in mouse spermatogenic cells

Abstract

Infertility has long been viewed as a predominantly female condition, even though half of infertility cases are attributed to the male partner. Despite this equal distribution of cases, the current medical understanding of and treatment options for male infertility are deeply lacking compared to that of females. This disparity not only causes there to be fewer options for treating males, but it also often places the burden of treatment for infertile males on their female partners, who may undergo procedures, such as assisted reproductive technology, and face its complications, even when she herself is fertile. This research project, performed in the Vigodner Lab, aims to help bridge this disparity and to contribute to the growing body of much-needed research on male infertility. Because male infertility is a multifactorial condition, continued research surrounding the key pathways involved in male infertility, such as the regulation of spermatogenesis, is imperative in the development of effective treatment options for infertile males. The Vigodner Lab’s research focuses on elucidating one means through which spermatogenesis is regulated – through SUMOylation. SUMOylation is a type of post-translational modification (PTM) in which a SUMO protein is bonded to a target protein in order to modify its function. A growing body of research supports the presence of crosstalk between SUMOylation and phosphorylation, a different type of PTM in which a phosphate group is added to a protein in order to modify it. The presence of this crosstalk in spermatocytes was previously studied in a 2-dimensional gel electrophoresis performed in the Vigodner Lab which analyzed the phosphoproteome of spermatocytes before and after inhibition of SUMOylation with GA. It identified several potential downstream targets of SUMOylation-dependent phosphorylation, including nucleophosmin. This research project confirmed that nucleophosmin is a downstream target of SUMOylation-dependent phosphorylation in mouse spermatocytes through the use of western blotting in both cell lines and primary cells.