Dctn5, a subunit of the dyactin complex for docking motor protein, may be involved in microtubule-dependent trafficking, which could participate in the immune response [1]. It may also be associated with various pathways related to different diseases such as those involving cell adhesion, mitochondrial and synaptic dynamics as indicated by transcriptome changes in certain mouse models [4].

In the Chinese tongue sole, Dctn5_tv1, one of its transcript variants, is widely distributed with high transcription in immune tissues. It can be up-regulated after Vibrio harveyi challenge and the recombinant form shows antimicrobial activity, suggesting its role in the immune response to bacterial invasion [1]. In cutaneous melanoma patients, low expression of Dctn5 is associated with favorable overall survival, indicating its potential as a prognostic biomarker [2]. In Wwtr1 -/- mice, which develop glomerulocystic kidney disease, the expression of Dctn5 is decreased, suggesting its involvement in maintaining renal cilia integrity [3]. In double-mutant mice with Pink1 ablation and A53T-SNCA overexpression, up-regulation of Dctn5 is observed, reflecting changes in multiple cellular dynamics [4]. An 8-gene signature including Dctn5 was found to be highly accurate for diagnosing ischemic stroke [5]. Also, knockdown of Dctn5, a bipolar disorder susceptibility gene, disrupts neuronal network physiology in vitro [6]. Additionally, a genetic variant associated with exercise intervention dropout is an expression quantitative trait locus of Dctn5 in skeletal muscle tissue [7].

In summary, Dctn5 plays crucial roles in immune responses, disease prognosis, renal cilia integrity, neuronal network physiology, and potentially in exercise-related genetic regulation. The findings from various animal models and in vitro studies contribute to understanding its functions in different disease areas such as melanoma, kidney diseases, neurodegeneration, stroke, and bipolar disorder.

References:

1. Wei, Min, Xu, Wen-Teng, Li, Kun-Ming, Zhao, Fa-Zhen, Chen, Song-Lin. 2018. Cloning, characterization and functional analysis of dctn5 in immune response of Chinese tongue sole (Cynoglossus semilaevis). In Fish & shellfish immunology, 77, 392-401. doi:10.1016/j.fsi.2018.04.007. https://pubmed.ncbi.nlm.nih.gov/29635065/

2. Wang, Qiaoqi, Wang, Xiangkun, Liang, Qian, Li, Dong, Pan, Fuqiang. 2018. Prognostic Value of Dynactin mRNA Expression in Cutaneous Melanoma. In Medical science monitor : international medical journal of experimental and clinical research, 24, 3752-3763. doi:10.12659/MSM.910566. https://pubmed.ncbi.nlm.nih.gov/29864111/

3. Hossain, Zakir, Ali, Safiah Mohamed, Ko, Hui Ling, Hong, Wanjin, Hunziker, Walter. 2007. Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1. In Proceedings of the National Academy of Sciences of the United States of America, 104, 1631-6. doi:. https://pubmed.ncbi.nlm.nih.gov/17251353/

4. Gispert, Suzana, Brehm, Nadine, Weil, Jonas, Roeper, Jochen, Auburger, Georg. 2014. Potentiation of neurotoxicity in double-mutant mice with Pink1 ablation and A53T-SNCA overexpression. In Human molecular genetics, 24, 1061-76. doi:10.1093/hmg/ddu520. https://pubmed.ncbi.nlm.nih.gov/25296918/

5. Feng, Bing, Meng, Xinling, Zhou, Hui, Wang, Hao, Zou, Donghua. 2021. Identification of Dysregulated Mechanisms and Potential Biomarkers in Ischemic Stroke Onset. In International journal of general medicine, 14, 4731-4744. doi:10.2147/IJGM.S327594. https://pubmed.ncbi.nlm.nih.gov/34456585/

6. MacLaren, Erik J, Charlesworth, Paul, Coba, Marcelo P, Grant, Seth G N. 2011. Knockdown of mental disorder susceptibility genes disrupts neuronal network physiology in vitro. In Molecular and cellular neurosciences, 47, 93-9. doi:10.1016/j.mcn.2010.12.014. https://pubmed.ncbi.nlm.nih.gov/21440632/

7. Jiang, Rong, Collins, Katherine A, Huffman, Kim M, Siegler, Ilene C, Kraus, William E. . Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease. In Annals of behavioral medicine : a publication of the Society of Behavioral Medicine, 58, 363-374. doi:10.1093/abm/kaae011. https://pubmed.ncbi.nlm.nih.gov/38489667/