Page 34 - GPD-2-2

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Multiple PDZ domain protein regulates sperm

motility through CatSper channel

2†
Dandan Wang 1,2† , Tinglong Zhang , Jianping Chen , Jingjing Huang , Jing Gu ,
1
2
1
3
Hao Liu , Yue Zhang , Xinying Ji 2,5,6 , Shaoping Ji *, and Jinyi Liu *
4
1
2
1 Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing
400038, China
2 Laboratory of Cell Signal Transduction, Henan Provincial Engineering Centre for Tumor Molecular
Medicine, School of Basic Medicine, Henan University, Kaifeng, Henan 475004, China
3 Queen Mary College, NanChang University, No.1299 Xuefu Avenue, Honggutan District, Nanchang,
Jiangxi 330031, China
4 Department of Obstetrics and Gynecology, 988 Hospital of PLA, 602 Zhengshanglu Ave,
Zhengzhou, Henan 450000, China
5 Kaifeng Municipal Key Laboratory for Infection and Biosafety, Henan International Joint Laboratory
of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University College of
Medicine, Kaifeng, Henan 475004, China
6 Faculty of Basic Medical Subjects, Shu-Qing Medical College of Zhengzhou, Mazhai, Erqi District,
Zhengzhou, Henan 450064, China

Abstract
† These authors contributed equally
to this work. Multiple PDZ domain protein (MPDZ) is a component of the crumbs cell polarity
complex and is ubiquitously expressed in mammalian tissues. In mouse sperm,
*Corresponding authors: MPDZ was identified as a regulator of the sperm acrosome reaction in the past two
Jinyi Liu
(jinyiliutmmu@163.com) decades. Here, a relationship between MPDZ and sperm motility was discovered.
Shaoping Ji During breeding, we found that MPDZ-null mice had smaller litter size. The Ca 2+
(shaopingji@henu.edu.cn) signal in mouse sperm decreased. Computer-assisted semen analysis revealed that
Citation: Wang D, Zhang T, Chen J, MPDZ-null males had reduced mouse sperm motility. In humans, MPDZ expression
et al., 2023, Multiple PDZ domain is positively associated with sperm motility. Considering the regulatory role of the
protein regulates sperm motility
through CatSper channel. Gene CatSper channel in sperm motility and fertility, we identified the expression profile
Protein Dis, 2(2):397. of CatSper subunits (CatSper1–4) and found a reduction at both the transcriptional
https://doi.org/10.36922/gpd.397 and translational levels in MPDZ-null mouse spermatozoa. However, in vitro,
Received: February 27, 2023 only CatSper1/2 expression was upregulated in MPDZ-overexpressing GC2 cells.
Accepted: June 20, 2023 Meanwhile, we found an upregulated cell Ca signal when MPDZ was overexpressed
2+
Published Online: June 30, 2023
in GC2 cells. Mechanical analysis revealed that MPDZ bound to the signal transducer
Copyright: © 2023 Author(s). and activator of transcription 3 (Stat3) and promoted its phosphorylation at
This is an Open Access article tyrosine 705 (Y705) to upregulate CatSper1/2 expression. Inhibition of Stat3 (Y705)
distributed under the terms of the
Creative Commons Attribution phosphorylation or Stat3 expression attenuated the effect of MPDZ on CatSper1/2
License, permitting distribution, expression. These results suggested that MPDZ was responsible for the transcriptional
and reproduction in any medium, regulation of the CatSper channel, at least in part, to regulate Ca signal and
2+
provided the original work is
properly cited. sperm motility. To the best of our knowledge, this is the first study to highlight the
importance of MPDZ acting as a regulator of sperm motility.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in

published maps and institutional Keywords: MPDZ; Sperm motility; CatSper; Stat3; Calciumsignal
affiliations.

Volume 2 Issue 2 (2023) 1 https://doi.org/10.36922/gpd.397