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ORIGINAL RESEARCH ARTICLE

Multiple PDZ domain protein regulates sperm motility through CatSper channel

Dandan Wang1,2† ,  Tinglong Zhang2† ,  Jianping Chen1 ,  Jingjing Huang2 ,  Jing Gu1 ,  Hao Liu3 ,  Yue Zhang4 ,  Xinying Ji2,5,6 ,  Shaoping Ji2* ,  Jinyi Liu1*
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1 Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, People’s Republic of China
2 Laboratory of Cell Signal Transduction, Henan Provincial Engineering Centre for Tumor Molecular Medicine, School of Basic Medicine, Henan University, Kaifeng 475004, People’s Republic of 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
GPD 2023, 2(2), 397 https://doi.org/10.36922/gpd.397
Submitted: 27 February 2023 | Accepted: 20 June 2023 | Published: 30 June 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Multiple PDZ domain protein (MPDZ) is a component of the crumbs cell polarity complex and is ubiquitously expressed in mammalian tissues. In mouse sperm, MPDZ was identified as a regulator of the sperm acrosome reaction in the past two decades. Here, a relationship between MPDZ and sperm motility was discovered. During breeding, we found that MPDZ-null mice had smaller litter size. The Ca2+ signal in mouse sperm decreased. Computer-assisted semen analysis revealed that MPDZ-null males had reduced mouse sperm motility. In humans, MPDZ expression is positively associated with sperm motility. Considering the regulatory role of the CatSper channel in sperm motility and fertility, we identified the expression profile of CatSper subunits (CatSper1–4) and found a reduction at both the transcriptional and translational levels in MPDZ-null mouse spermatozoa. However, in vitro, only CatSper1/2 expression was upregulated in MPDZ-overexpressing GC2 cells. Meanwhile, we found an upregulated cell Ca2+ signal when MPDZ was overexpressed in GC2 cells. Mechanical analysis revealed that MPDZ bound to the signal transducer and activator of transcription 3 (Stat3) and promoted its phosphorylation at tyrosine 705 (Y705) to upregulate CatSper1/2 expression. Inhibition of Stat3 (Y705) phosphorylation or Stat3 expression attenuated the effect of MPDZ on CatSper1/2 expression. These results suggested that MPDZ was responsible for the transcriptional regulation of the CatSper channel, at least in part, to regulate Ca2+ signal and 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.

Keywords
MPDZ
Sperm motility
CatSper
Stat3
Calcium signal
Funding
Natural Science Foundation Project of Chongqing CSTC of China
National Natural Science Foundation of China
Conflict of interest
The authors declare no conflict of interest.
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