PITHD1 is essential for male fertilization
近藤, 博之 徳島大学大学院医科学教育部（医学専攻）
Matsumura, Takafumi Osaka University|Yokohama City University
Kaneko, Mari RIKEN
Inoue, Kenichi RIKEN
Ikawa, Masahito Osaka University
The proteasome is a protein-degrading molecular complex that is necessary for protein homeostasis and various biological functions, including cell cycle regulation, signal transduction, and immune response. Proteasome activity is finely regulated by a variety of proteasome-interacting molecules. PITHD1 is a recently described molecule that has a domain putatively capable of interacting with the proteasome. However, it is unknown as to whether PITHD1 can actually bind to proteasomes and what it does in vivo. Here we report that PITHD1 is detected specifically in the spermatids in the testis and the cortical thymic epithelium in the thymus. Interestingly, PITHD1 associates with immunoproteasomes in the testis, but not with thymoproteasomes in the thymus. Mice deficient in PITHD1 exhibit severe male infertility accompanied with morphological abnormalities and impaired motility of spermatozoa. Furthermore, PITHD1 deficiency reduces proteasome activity in the testis and alters the amount of proteins that are important for fertilization capability by the sperm. However, the PITHD1-deficient mice demonstrate no detectable defects in the thymus, including T cell development. Collectively, our results identify PITHD1 as a proteasome-interacting protein that plays a nonredundant role in the male reproductive system.
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
This research was originally published in the Journal of Biological Chemistry. Hiroyuki Kondo, Takafumi Matsumura, Mari Kaneko, Kenichi Inoue, Hidetaka Kosako, Masahito Ikawa, Yousuke Takahama, Izumi Ohigashi. PITHD1 is a proteasome-interacting protein essential for male fertilization. J Biol Chem. 2020, 295(6):1658-1672.
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