Gga1-KO Mouse

Gga1, also known as Golgi-localized, gamma adaptin ear-containing, ARF-binding protein 1, is involved in protein trafficking processes. It has been associated with the Golgi apparatus and endosomal functions, playing a role in various biological pathways such as spermatogenesis, myogenesis, and the regulation of endosome acidification and maturation [1,2,3,4]. Genetic models like knockout mice are valuable tools to study its functions.

In mice, Gga1 knockout male mice had normal fertility under normal conditions. However, when exposed to bisphenol A (BPA), Gga1 ablation led to infertility, along with reduced sperm count, motility, and percentage of normal sperm, suggesting Gga1 protects spermatogenesis against BPA-induced damage [1]. In Gga1 knockout cells, the endosomal Na⁺/H⁺ exchanger NHE6 was mislocalized, with less in endosomes, more transported to lysosomes, and more retained in the Golgi, accompanied by Golgi lumen alkalinization, indicating Gga1-NHE6 interaction functions in NHE6 localization to the endosome compartment [2,3]. In C2C12 myoblasts, Gga1 depletion prevented the formation of large multi-nucleated myotubes, and GGA1 was involved in the cell-surface expression and sorting of the insulin receptor, playing a significant role in myotube formation and maturation [4].

In conclusion, Gga1 is essential for maintaining normal spermatogenesis under stress, regulating the localization of endosomal transporters like NHE6, and facilitating myotube formation. The use of Gga1 knockout mouse models has provided insights into its role in these processes, contributing to our understanding of male infertility, neurological disorders related to NHE6 mutations, and muscle development.

References:

1. Jiao, Haoyun, Chen, Yinghong, Han, Tingting, Gao, Fei, Li, Guoping. 2023. GGA1 participates in spermatogenesis in mice under stress. In PeerJ, 11, e15673. doi:10.7717/peerj.15673. https://pubmed.ncbi.nlm.nih.gov/37551344/

2. Ma, Li, Kasula, Ravi Kiran, Ouyang, Qing, Schmidt, Michael, Morrow, Eric M. 2024. GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment. In The Journal of biological chemistry, 300, 107552. doi:10.1016/j.jbc.2024.107552. https://pubmed.ncbi.nlm.nih.gov/39002678/

3. Ma, Li, Kasula, Ravi Kiran, Ouyang, Qing, Schmidt, Michael, Morrow, Eric M. 2023. GGA1 interacts with the endosomal Na+/H+ Exchanger NHE6 governing localization to the endosome compartment. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.11.08.565997. https://pubmed.ncbi.nlm.nih.gov/37986849/

4. Isobe, Mari, Lee, Sachiko, Waguri, Satoshi, Kametaka, Satoshi. 2018. Clathrin adaptor GGA1 modulates myogenesis of C2C12 myoblasts. In PloS one, 13, e0207533. doi:10.1371/journal.pone.0207533. https://pubmed.ncbi.nlm.nih.gov/30440034/