Ask about this productRelated genes to: CCDC38 antibody
- Gene:
- CCDC38 NIH gene
- Name:
- coiled-coil domain containing 38
- Previous symbol:
- -
- Synonyms:
- FLJ40089
- Chromosome:
- 12q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 2005-11-02
- Date modifiied:
- 2016-11-09
Related products to: CCDC38 antibody
Related articles to: CCDC38 antibody
- Multiple morphological abnormalities of the flagella (MMAF) is a severe disease of male infertility, while the pathogenetic mechanisms of MMAF are still incompletely understood. Previously, we found that the deficiency of Ccdc38 might be associated with MMAF. To understand the underlying mechanism of this disease, we identified the potential partner of this protein and found that the coiled-coil domain containing 146 (CCDC146) can interact with CCDC38. It is predominantly expressed in the testes, and the knockout of this gene resulted in complete infertility in male mice but not in females. The knockout of Ccdc146 impaired spermiogenesis, mainly due to flagellum and manchette organization defects, finally led to MMAF-like phenotype. Furthermore, we demonstrated that CCDC146 could interact with both CCDC38 and CCDC42. It also interacts with intraflagellar transport (IFT) complexes IFT88 and IFT20. The knockout of this gene led to the decrease of ODF2, IFT88, and IFT20 protein levels, but did not affect CCDC38, CCDC42, or ODF1 expression. Additionally, we predicted and validated the detailed interactions between CCDC146 and CCDC38 or CCDC42, and built the interaction models at the atomic level. Our results suggest that the testis predominantly expressed gene Ccdc146 is essential for sperm flagellum biogenesis and male fertility, and its mutations might be associated with MMAF in some patients. - Source: PubMed
Publication date: 2023/12/01
Ma YanjieWu BingbingChen YinghongMa ShuangWang LiyingHan TingtingLin XiaoleiYang FulinLiu ChaoZhao JianguoLi Wei - During spermiogenesis, haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes, which are required for successful fertilization. Severe deformities in flagella cause a male infertility syndrome, multiple morphological abnormalities of the flagella (MMAF), while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental potential. However, evidence regarding the occurrence of acrosomal hypoplasia in MMAF is limited. Here, we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38 (Ccdc38) via inducing a nonsense mutation and find that the males are infertile. The Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF phenotypes. We find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO sperm. Further analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3, a protein associated with acrosome biogenesis, in testes and an aberrant distribution of TEKT3 in sperm. We finally show that intracytoplasmic sperm injection overcomes Ccdc38-related infertility. Our study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF. - Source: PubMed
Publication date: 2023/09/13
Wang YalingHuang XueyingSun GuoyingChen JingwenWu BangguoLuo JiahuiTang ShuyanDai PengZhang FengLi JinsongWang Lingbo - The sperm flagellum is essential for male fertility, and defects in flagellum biogenesis are associated with male infertility. Deficiency of coiled-coil domain-containing (CCDC) 42 (CCDC42) is specifically associated with malformation of mouse sperm flagella. Here, we find that the testis-specific protein CCDC38 interacts with CCDC42, localizing on the manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in a distorted manchette, multiple morphological abnormalities of the flagella of spermatozoa and eventually male sterility. Furthermore, we find that CCDC38 interacts with intraflagellar transport protein 88 (IFT88), as well as outer dense fibrous 2 (ODF2), and the knockout of Ccdc38 reduces transport of ODF2 to the flagellum. Altogether, our results uncover the essential role of CCDC38 in sperm flagellum biogenesis, and suggest that some mutations of these genes might be associated with male infertility in humans. - Source: PubMed
Publication date: 2022/06/13
Zhang RuidanWu BingbingLiu ChaoZhang ZheWang XiugeWang LiyingXiao SaiChen YinghongWei HuafangJiang HuiGao FeiYuan LiLi Wei - Sperm fibrous sheath, a unique cytoskeletal structure, is implicated in various sperm physiological functions, such as sperm maturation, motility and capacitation. AKAP4 has been described to be required for structural and functional integrity of the fibrous sheath. We generated Akap4-knockout mice line using CRISPR-Cas9 system. Cytomorphology and motility of sperm and testes were studied, confirming loss of Akap4 led to abnormal sperm morphology, motility and infertility. The proteomic components of testes were studied and Akap4 was found to be significantly decreased in the Akap4-knockout mice. Testis single-cell RNA sequencing and analysis revealed three genes with significant change in the general cell population, i.e., Akap4, Haspin, and Ccdc38. The single-cell RNA expression profiles also showed that the major difference between Akap4-knockout and wild-type testes existed in the elongating cell cluster, where in the Akap4-knockout testes, a subgroup of elongating cells with marker genes involved in cell adhesion and migration were increased, while a subgroup of elongating cells marked by mitochondrial sheath genes were decreased. Our results revealed the complex and well-coordinated procedures of spermatogenesis, and substantiated Akap4's indispensable roles in the integrity of sperm flagellum and the step-wise maturation of spermatozoa. - Source: PubMed
Publication date: 2019/06/28
Fang XiangHuang Ling-LongXu JianMa Cai-QiChen Zhi-HengZhang ZhanLiao Cai-HuaZheng Shu-XinHuang PengXu Wen-MingLi NaSun Ling - Distinguishing the testes-specific genes in different species may disclose key genes associated with testes-specific functions and provide sufficient information for the study and treatment of male infertility. A testes‑specific gene, coiled-coil domain containing 38 (Ccdc38), was identified by screening UniGene libraries. Systematic bioinformatics analysis demonstrated that the CCDC38 protein was conserved in various mammalian species. It was determined that CCDC38 was exclusively expressed in testes and its expression increased from 2‑8 weeks of age. Additional immunohistochemical analysis indicated that CCDC38 was mainly expressed in spermatogonia and spermatocytes. It is of note that, immunofluorescence and co-immunoprecipitation assays demonstrated that CCDC38 interacted with ubiquitinated histone H2A in mouse testes. Therefore, these results suggest that Ccdc38 is a testes-specific gene, which may be important for mouse spermatogenesis. - Source: PubMed
Publication date: 2016/06/03
Lin Shou-RenLi Yu-ChiLuo Man-LingGuo HuanWang Tian-TianChen Jian-BoMa QianGu Yan-LiJiang Zhi-MaoGui Yao-Ting