Oncotarget

Research Papers:

CCR6 is required for ligand-induced CatSper activation in human sperm

Ruiying Diao, Tao Wang, Kin Lam Fok, Xiaofeng Li, Yechun Ruan, Mei Kuen Yu, Yimin Cheng, Ying Chen, Hao Chen, Lisha Mou, Xueyong Cai, Yan Wang, Zhiming Cai, Xuhui Zeng and Hsiao Chang Chan _

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Oncotarget. 2017; 8:91445-91458. https://doi.org/10.18632/oncotarget.20651

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Abstract

Ruiying Diao1,*, Tao Wang2,*, Kin Lam Fok3,*, Xiaofeng Li3, Yechun Ruan3,4, Mei Kuen Yu3, Yimin Cheng2, Ying Chen2, Hao Chen1,3, Lisha Mou1, Xueyong Cai1, Yan Wang3, Zhiming Cai1, Xuhui Zeng2 and Hsiao Chang Chan3,5

1Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China

2Institute of Life Science and School of Life Science, Nanchang University, Nanchang, China

3Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China

4Interdisciplinary Division of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China

5Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China

*These authors have contributed equally to this work

Correspondence to:

Hsiao Chang Chan, email: [email protected]

Xuhui Zeng, email: [email protected]

Zhiming Cai, email: [email protected]

Keywords: CCR6, CatSper, human β-defensin-1, progesterone, sperm

Received: May 26, 2017    Accepted: July 13, 2017    Published: September 05, 2017

ABSTRACT

CatSper channel has been considered the principal sperm Ca2+ channel responsible for the cytosolic Ca2+ elevation required for various sperm functions necessary for fertilization [1–4]. However, the mechanism underlying the activation of CatSper channel by various physiological ligands remain incompletely understood. We have recently demonstrated the expression of C-C chemokine receptor 6 (CCR6) in sperm and Ca2+ influx upon binding of human β-defensin 1 (DEFB1) to CCR6, which is important for sperm motility [5]. In the present study, we have demonstrated that CCR6 receptor and CatSper channel are both required for the Ca2+ entry/current induced by physiological ligands DEFB1, chemokine (C-C motif) ligand 20 (CCL20) and progesterone in human sperm. CCR6 is co-localized and interacts with CatSper in human sperm. Ca2+ influx mediated by CCR6 and CatSper is required for essential sperm functions, including motility, hyperactivation and acrosome reaction, which are impaired in infertile sperm showing reduced levels of CCR6 and CatSper. The present finding suggests a critical role of CCR6 receptor in mediating ligand-induced, CatSper-dependent Ca2+ influx required for various sperm functions and thus male fertility.


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PII: 20651