PITHD1 is a proteasome-interacting protein essential for male fertilization

Kondo, Hiroyuki; Matsumura, Takafumi; Kaneko, Mari et al.

Journal of Biological Chemistry, 2020, 295(6), 1658-1672

Number of Access:842（2025-08-22 02:09 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78549

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Title
PITHD1 is a proteasome-interacting protein essential for male fertilization
Creator
CreatorName
Kondo, Hiroyuki
CreatorName
Matsumura, Takafumi
CreatorName
Kaneko, Mari
CreatorName
Inoue, Kenichi
NRID
1000010291171 1000010291171
CreatorName
Kosako, Hidetaka
NRID
1000020304066 1000020304066
ORCID
0000-0001-9859-6217 0000-0001-9859-6217
researchmap permalink
read0054910 read0054910
Scopus Author ID
16689054500 16689054500
CreatorName
Ikawa, Masahito
NRID
1000020183858 1000020183858
CreatorName
Takahama, Yousuke
NRID
1000000596588 1000000596588
CreatorName
Ohigashi, Izumi
Description
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, Journal of Biological Chemistry, Volume 295, Issue 6, 2020, Pages 1658-1672, ISSN 0021-9258, https://doi.org/10.1074/jbc.RA119.011144.
Abstract
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 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 identifyPITHD1as a proteasome- interacting protein that plays a nonredundant role in the male reproductive system.
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Source Title
Journal of Biological Chemistry
Volume (Issue)
295(6)
Page
1658-1672
Date of Issued
2020-02-07
Language
English
Handle URL
https://hdl.handle.net/11094/78549
PISSN
00219258
eISSN
1083351X
NCID
AA1202441X
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1074/jbc.RA119.011144
PMID
31915251
Access Rights
open access
CopyRight
© 2020 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article