PITHD1 is a proteasome-interacting protein essential for male fertilization

• Material Type: 博士論文
• Title: PITHD1 is a proteasome-interacting protein essential for male fertilization
• Author/Editor: Kondo, Hiroyuki; Matsumura, Takafumi; Kaneko, Mari; Inoue, Kenichi; Kosako, Hidetaka; Ikawa, Masahito; Takahama, Yousuke; Ohigashi, Izumi
• Author Heading: Kondo, Hiroyuki; Matsumura, Takafumi; Kaneko, Mari; Inoue, Kenichi; Kosako, Hidetaka; Ikawa, Masahito; Takahama, Yousuke; Ohigashi, Izumi
• Publication, Distribution, etc.: American Society for Biochemistry and Molecular Biology
• Publication Date: 2020-01-08
• Publication Date (W3CDTF): 2020-01-08
• Alternative Title: 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
• Periodical title: Journal of Biological Chemistry
• No. or year of volume/issue: 295 6
• Volume: 295
• Issue: 6
• Pages: 1658-1672
• ISSN (Periodical Title): ISSN : 1083-351X
• Degree grantor/type: 徳島大学
• Date Granted: 2020-02-27
• Dissertation Number: 甲第3360号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: proteasome; thymus; epithelial cell; testis; sperm; fertilization
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): © the Author(s).
• Related Material (DOI): 10.1074/jbc.RA119.011144
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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