Drg2, or developmentally regulated GTP-binding protein 2, is an evolutionarily conserved GTP-binding protein. It is involved in multiple biological processes, including cell growth, inflammation, mitochondria dynamics, and regulation of microtubule stability [4,3,7]. It may also play a role in various signaling pathways related to cell cycle progression, immune response, and angiogenesis [8,2,1]. Genetic models, such as knockout (KO) mice, have been crucial in studying its functions.

In KO mouse models, DRG2 deficiency has diverse effects. In endothelial cells, it promotes senescence and dysfunction, reducing angiogenic capability and increasing oxidative stress [1]. In macrophages, it impairs the initial inflammatory response against Listeria monocytogenes infection [2]. In melanoma, DRG2 depletion inhibits primary tumor growth and metastasis by reducing VEGF-A expression [5]. In the brain, DRG2 knockout leads to impaired motor behaviors with reduced striatal dopamine release [6]. In HeLa cells, DRG2 knockdown affects microtubule dynamics, Golgi stacking, and cell migration, as well as G2/M phase progression in the cell cycle [7,3,8].

In conclusion, Drg2 is a key regulator in multiple biological processes. Studies using KO mouse models have revealed its significance in vascular dysfunction, infectious diseases, cancer, and neurological disorders. Understanding Drg2 functions provides insights into the mechanisms of these diseases, potentially offering new strategies for treatment and prevention.

References:

1. Le, Anh-Nhung, Park, Seong-Soon, Le, Minh-Xuan, Ha, Chang Man, Park, Jeong Woo. 2022. DRG2 Depletion Promotes Endothelial Cell Senescence and Vascular Endothelial Dysfunction. In International journal of molecular sciences, 23, . doi:10.3390/ijms23052877. https://pubmed.ncbi.nlm.nih.gov/35270019/

2. Lee, Unn Hwa, Park, Sang Jin, Ju, Seong A, Cho, Wha Ja, Park, Jeong Woo. 2023. DRG2 in macrophages is crucial for initial inflammatory response and protection against Listeria monocytogenes infection. In Clinical immunology (Orlando, Fla.), 257, 109819. doi:10.1016/j.clim.2023.109819. https://pubmed.ncbi.nlm.nih.gov/37918467/

3. Mani, Muralidharan, Thao, Dang Thi, Kim, Beom Chang, Han, In-Seob, Park, Jeong Woo. 2019. DRG2 knockdown induces Golgi fragmentation via GSK3β phosphorylation and microtubule stabilization. In Biochimica et biophysica acta. Molecular cell research, 1866, 1463-1474. doi:10.1016/j.bbamcr.2019.06.003. https://pubmed.ncbi.nlm.nih.gov/31199931/

4. Li, Bing Si, Jin, Ai Lin, Zhou, ZiQi, Seo, Jae Ho, Choi, Byung-Min. 2021. DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts. In Oxidative medicine and cellular longevity, 2021, 7301373. doi:10.1155/2021/7301373. https://pubmed.ncbi.nlm.nih.gov/34777693/

5. Yoon, Nal Ae, Jung, Se Jin, Choi, Seong Hee, Cha, Hee Jeong, Park, Jeong Woo. 2019. DRG2 supports the growth of primary tumors and metastases of melanoma by enhancing VEGF-A expression. In The FEBS journal, 287, 2070-2086. doi:10.1111/febs.15125. https://pubmed.ncbi.nlm.nih.gov/31693298/

6. Lim, Hye Ryeong, Vo, Mai-Tram, Kim, Dong Jun, Park, Jeong Woo, Ha, Chang Man. 2019. DRG2 Deficient Mice Exhibit Impaired Motor Behaviors with Reduced Striatal Dopamine Release. In International journal of molecular sciences, 21, . doi:10.3390/ijms21010060. https://pubmed.ncbi.nlm.nih.gov/31861806/

7. Dang, Thao, Jang, Soo Hwa, Back, Sung Hoon, Park, Jeong Woo, Han, In-Seob. 2018. DRG2 Deficiency Causes Impaired Microtubule Dynamics in HeLa Cells. In Molecules and cells, 41, 1045-1051. doi:10.14348/molcells.2018.0129. https://pubmed.ncbi.nlm.nih.gov/30453731/

8. Jang, Soo Hwa, Kim, Ah-Ram, Park, Neung-Hwa, Park, Jeong Woo, Han, In-Seob. 2016. DRG2 Regulates G2/M Progression via the Cyclin B1-Cdk1 Complex. In Molecules and cells, 39, 699-704. doi:10.14348/molcells.2016.0149. https://pubmed.ncbi.nlm.nih.gov/27669826/