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ID 114611
タイトル別表記
精巣内プロテアソームに会合する分子PITHD1の機能解析
PITHD1 is essential for male fertilization
著者
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
キーワード
proteasome
thymus
epithelial cell
testis
sperm
fertilization
資料タイプ
学位論文
抄録
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.
掲載誌名
Journal of Biological Chemistry
ISSN
1083351X
cat書誌ID
AA1202441X
出版者
American Society for Biochemistry and Molecular Biology
295
6
開始ページ
1658
終了ページ
1672
発行日
2020-01-08
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Hiroyuki Kondoの学位論文として提出され,学位審査・授与の対象となっている。
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.
権利情報
© the Author(s).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3360号
学位記番号
甲医第1443号
学位授与年月日
2020-02-27
学位名
博士(医学)
学位授与機関
徳島大学
部局
先端酵素学研究所