Pacrg, the Parkin co-regulated gene, shares a bidirectional promoter with the Parkinson's disease-associated gene Parkin. It is involved in multiple biological processes. In cilia and flagella, it plays a role in axoneme formation and ciliary motility, and is also associated with sperm development, cellular signaling, and TNF signaling pathways [2,3,4,5]. Genetic models, especially mouse models, have been crucial in studying its functions.

In mice, a specific deficiency of DNALI1, which recruits and stabilizes PACRG, leads to male infertility due to abnormal sperm morphology and impaired spermiogenesis. This indicates that the MEIG1/PACRG complex within the manchette, required for sperm flagellum assembly, depends on DNALI1 [1]. In Meig1-deficient mice, PACRG localization in the manchette remains unchanged, while in Pacrg-deficient mice, MEIG1 no longer localizes to the manchette, suggesting that PACRG recruits MEIG1 to this structure for sperm flagella building [6].

In conclusion, Pacrg is essential for sperm flagellum assembly and male fertility as demonstrated by gene-knockout mouse models. It also plays significant roles in ciliary motility, cellular signaling, and TNF signaling. Understanding Pacrg's functions provides insights into the mechanisms of sperm development and related biological processes, as well as potential implications for diseases associated with its dysregulation [1,2,4,5,6].

References:

1. 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/

2. Dymek, Erin E, Lin, Jianfeng, Fu, Gang, Nicastro, Daniela, Smith, Elizabeth F. 2019. PACRG and FAP20 form the inner junction of axonemal doublet microtubules and regulate ciliary motility. In Molecular biology of the cell, 30, 1805-1816. doi:10.1091/mbc.E19-01-0063. https://pubmed.ncbi.nlm.nih.gov/31116684/

3. Hasse, Timothy, Zhang, Zhibing, Huang, Yu-Ming M. 2022. Molecular dynamics study reveals key disruptors of MEIG1-PACRG interaction. In Proteins, 91, 555-566. doi:10.1002/prot.26449. https://pubmed.ncbi.nlm.nih.gov/36444670/

4. Loucks, Catrina M, Bialas, Nathan J, Dekkers, Martijn P J, Jansen, Gert, Leroux, Michel R. 2016. PACRG, a protein linked to ciliary motility, mediates cellular signaling. In Molecular biology of the cell, 27, 2133-44. doi:10.1091/mbc.E15-07-0490. https://pubmed.ncbi.nlm.nih.gov/27193298/

5. Meschede, Jens, Šadić, Maria, Furthmann, Nikolas, Tatzelt, Jörg, Winklhofer, Konstanze F. 2020. The parkin-coregulated gene product PACRG promotes TNF signaling by stabilizing LUBAC. In Science signaling, 13, . doi:10.1126/scisignal.aav1256. https://pubmed.ncbi.nlm.nih.gov/32019898/

6. Li, Wei, Tang, Waixing, Teves, Maria E, Strauss, Jerome F, Zhang, Zhibing. . A MEIG1/PACRG complex in the manchette is essential for building the sperm flagella. In Development (Cambridge, England), 142, 921-30. doi:10.1242/dev.119834. https://pubmed.ncbi.nlm.nih.gov/25715396/