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ID 114611
Title Alternative
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
Author
Kondo, Hiroyuki Tokushima University
Matsumura, Takafumi Osaka University|Yokohama City University
Kaneko, Mari RIKEN
Inoue, Kenichi RIKEN
Ikawa, Masahito Osaka University
Keywords
proteasome
thymus
epithelial cell
testis
sperm
fertilization
Content Type
Thesis or Dissertation
Description
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 Title
Journal of Biological Chemistry
ISSN
1083351X
NCID
AA1202441X
Publisher
American Society for Biochemistry and Molecular Biology
Volume
295
Issue
6
Start Page
1658
End Page
1672
Published Date
2020-01-08
Remark
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.
Rights
© the Author(s).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3360号
Diploma Number
甲医第1443号
Granted Date
2020-02-27
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Institute of Advanced Medical Sciences