DNALI1, short for axonemal dynein light intermediate polypeptide 1, is a component of axonemal dyneins. Axonemal dyneins are motor protein complexes crucial for the movement of eukaryotic cilia and flagella. Thus, DNALI1 is important for processes related to ciliary and flagellar functions. It has been associated with pathways involved in cell differentiation during spermatogenesis and autophagy regulation [1-3, 5, 9, 10]. Genetic models, like mouse models, have been valuable in studying its functions.

In mice, specific deficiency of DNALI1 in male germ cells led to a dramatic reduction in sperm cells, abnormal sperm morphology, and male infertility, emphasizing its role in sperm differentiation and flagellum assembly [2]. DNALI1-mutated male mice had impaired sperm motility due to disrupted ultrastructure of sperm flagellum [4]. In a CTE model, DNALI1 silencing enhanced autophagic flux and alleviated neurodegeneration, while its overexpression inhibited autophagosome-lysosome fusion, reduced autophagic flux, and exacerbated cell death under pathological conditions [1]. In humans, DNALI1 mutations caused male infertility with severe asthenozoospermia by disrupting the assembly of flagellar inner dynein arms and fibrous sheath [3,5,6].

In conclusion, DNALI1 is essential for sperm development, motility, and male fertility, likely through its role in flagellum assembly and the formation of relevant protein complexes. In the context of traumatic brain injury, it has a significant impact on neurodegeneration by regulating autophagic flux. The study of DNALI1 using gene-knockout mouse models has provided key insights into male infertility and post-TBI neurodegeneration, offering potential targets for related disease treatments.

References:

1. Ding, Xulong, Cao, Shuqiang, Wang, Qing, Liang, Weibo, Lei, Peng. 2024. DNALI1 Promotes Neurodegeneration after Traumatic Brain Injury via Inhibition of Autophagosome-Lysosome Fusion. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2306399. doi:10.1002/advs.202306399. https://pubmed.ncbi.nlm.nih.gov/38348540/

2. Yap, Yi Tian, Li, Wei, Huang, Qian, Toure, Aminata, Zhang, Zhibing. 2023. DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice. In eLife, 12, . doi:10.7554/eLife.79620. https://pubmed.ncbi.nlm.nih.gov/37083624/

3. Wu, Huan, Liu, Yiyuan, Li, Yuqian, He, Xiaojin, Cao, Yunxia. 2023. DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath. In Cell death & disease, 14, 127. doi:10.1038/s41419-023-05653-y. https://pubmed.ncbi.nlm.nih.gov/36792588/

4. Zhou, Yiling, Wang, Yaling, Chen, Jingwen, Liu, Chunyu, Wang, Lingbo. 2023. Dnali1 is required for sperm motility and male fertility in mice. In Basic and clinical andrology, 33, 32. doi:10.1186/s12610-023-00205-y. https://pubmed.ncbi.nlm.nih.gov/37993789/

5. Sha, Yanwei, Liu, Wensheng, Nie, Hua, Jiang, Xiaoming, Wei, Xiaoli. 2023. Homozygous mutation in DNALI1 leads to asthenoteratozoospermia by affecting the inner dynein arms. In Frontiers in endocrinology, 13, 1058651. doi:10.3389/fendo.2022.1058651. https://pubmed.ncbi.nlm.nih.gov/36726469/

6. Zhang, Fengbin, Li, Jingping, Liang, Zhongyan, Chen, Weikang, Li, Lejun. 2024. Splicing Mutation in DNALI1 Causes Male Infertility with Severe Oligoasthenoteratozoospermia in Humans. In Reproductive sciences (Thousand Oaks, Calif.), 31, 1610-1616. doi:10.1007/s43032-023-01451-1. https://pubmed.ncbi.nlm.nih.gov/38212584/