Arfgap3, short for ADP ribosylation factor GTPase-activating protein 3, is a member of ArfGAPs. It plays a crucial role in regulating the vesicular trafficking pathway, especially in COPI coat assembly [1,2,4,5,6,7]. It is involved in intracellular protein transport and is associated with the Golgi apparatus. Genetic models, such as mouse models, have been instrumental in understanding its functions.

In skeletal muscle, Arfgap3 is expressed during injury repair and myoblast differentiation. Knockdown of Arfgap3 in C2C12 myoblasts blocked intracellular vesicle transport and glucose uptake, impaired myoblast proliferation under low-glucose conditions, increased apoptosis, and hindered myotube differentiation, suggesting its role in modulating the skeletal muscle repair process [1]. In ageing skeletal muscle, Arfgap3 expression was downregulated. Knockdown of Arfgap3 in an ageing C2C12 model exacerbated impaired differentiation and mitochondrial damage, while overexpression mitigated these effects, indicating its role in protecting mitochondrial function and promoting autophagy through Rab5a-mediated signals [2]. In prostate cancer cells, ARFGAP3 (Arfgap3 in androgen-sensitive LNCaP cells) promoted cell proliferation and migration, and knockdown of it reduced LNCaP cell growth [3]. In post-Golgi traffic, downregulation of Arfgap3 affected the localization of cation-independent mannose 6-phosphate receptor, perturbed retrograde transport, and slowed the degradation of epidermal growth factor receptor after stimulation [4].

In summary, Arfgap3 is essential for vesicular trafficking and intracellular protein transport. Its functions are revealed through various model-based studies, with implications in multiple disease areas. In skeletal muscle, it impacts injury repair, and in ageing muscle, it affects mitochondrial function and autophagy. In prostate cancer, it is involved in cancer cell proliferation and migration. These findings highlight the significance of Arfgap3 in understanding biological processes and disease mechanisms [1,2,3].

References:

1. Li, Suting, Wang, Zhi, Chen, Mao, Tang, Jianming, Hong, Li. 2022. ArfGAP3 regulates vesicle transport and glucose uptake in myoblasts. In Cellular signalling, 103, 110551. doi:10.1016/j.cellsig.2022.110551. https://pubmed.ncbi.nlm.nih.gov/36476390/

2. Chen, Mao, Huang, Xiaoyu, Li, Bingshu, Zhang, Shufei, Hong, Li. . ArfGAP3 Protects Mitochondrial Function and Promotes Autophagy Through Rab5a-Mediated Signals in Ageing Skeletal Muscle. In Journal of cachexia, sarcopenia and muscle, 16, e13725. doi:10.1002/jcsm.13725. https://pubmed.ncbi.nlm.nih.gov/39961359/

3. Obinata, Daisuke, Takayama, Ken-ichi, Urano, Tomohiko, Takahashi, Satoru, Inoue, Satoshi. 2011. ARFGAP3, an androgen target gene, promotes prostate cancer cell proliferation and migration. In International journal of cancer, 130, 2240-8. doi:10.1002/ijc.26224. https://pubmed.ncbi.nlm.nih.gov/21647875/

4. Shiba, Yoko, Kametaka, Satoshi, Waguri, Satoshi, Presley, John F, Randazzo, Paul Agostino. 2013. ArfGAP3 regulates the transport of cation-independent mannose 6-phosphate receptor in the post-Golgi compartment. In Current biology : CB, 23, 1945-51. doi:10.1016/j.cub.2013.07.087. https://pubmed.ncbi.nlm.nih.gov/24076238/

5. Liu, X, Zhang, C, Xing, G, Chen, Q, He, F. . Functional characterization of novel human ARFGAP3. In FEBS letters, 490, 79-83. doi:. https://pubmed.ncbi.nlm.nih.gov/11172815/

6. Kartberg, Fredrik, Asp, Lennart, Dejgaard, Selma Y, Nilsson, Tommy, Presley, John F. 2010. ARFGAP2 and ARFGAP3 are essential for COPI coat assembly on the Golgi membrane of living cells. In The Journal of biological chemistry, 285, 36709-20. doi:10.1074/jbc.M110.180380. https://pubmed.ncbi.nlm.nih.gov/20858901/

7. Weimer, Carolin, Beck, Rainer, Eckert, Priska, Brügger, Britta, Wieland, Felix. . Differential roles of ArfGAP1, ArfGAP2, and ArfGAP3 in COPI trafficking. In The Journal of cell biology, 183, 725-35. doi:10.1083/jcb.200806140. https://pubmed.ncbi.nlm.nih.gov/19015319/