DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis.
10.1007/s11684-021-0851-8
- Author:
Xiuli ZHANG
1
;
Zhizhou XIA
1
;
Xingyu LV
2
;
Donghe LI
1
;
Mingzhu LIU
1
;
Ruihong ZHANG
1
;
Tong JI
3
;
Ping LIU
4
;
Ruibao REN
5
Author Information
1. Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
2. Key Laboratory of Laparoscopic Technology of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
3. Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. jitong@zju.edu.cn.
4. Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. liupingjize@126.com.
5. Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. rbren@sjtu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Dcaf8;
male infertility;
spermatogenesis
- MeSH:
Animals;
Cullin Proteins/genetics*;
DNA-Binding Proteins/genetics*;
Factor VIII;
Male;
Mice;
Mice, Knockout;
Spermatogenesis/genetics*;
Ubiquitin-Protein Ligases
- From:
Frontiers of Medicine
2021;15(2):302-312
- CountryChina
- Language:English
-
Abstract:
Cullin-RING E3 ubiquitin ligase (CRL)-4 is a member of the large CRL family in eukaryotes. It plays important roles in a wide range of cellular processes, organismal development, and physiological and pathological conditions. DDB1- and CUL4-associated factor 8 (DCAF8) is a WD40 repeat-containing protein, which serves as a substrate receptor for CRL4. The physiological role of DCAF8 is unknown. In this study, we constructed Dcaf8 knockout mice. Homozygous mice were viable with no noticeable abnormalities. However, the fertility of Dcaf8-deficient male mice was markedly impaired, consistent with the high expression of DCAF8 in adult mouse testis. Sperm movement characteristics, including progressive motility, path velocity, progressive velocity, and track speed, were significantly lower in Dcaf8 knockout mice than in wild-type (WT) mice. However, the total motility was similar between WT and Dcaf8 knockout sperm. More than 40% of spermatids in Dcaf8 knockout mice showed pronounced morphological abnormalities with typical bent head malformation. The acrosome and nucleus of Dcaf8 knockout sperm looked similar to those of WT sperm. In vitro tests showed that the fertilization rate of Dcaf8 knockout mice was significantly reduced. The results demonstrated that DCAF8 plays a critical role in spermatogenesis, and DCAF8 is a key component of CRL4 function in the reproductive system.
