Arl4d, an ADP-ribosylation factor (Arf)-like 4D small GTPase, is involved in multiple biological processes. It functions in the regulation of cell morphology, cell migration, and actin cytoskeleton remodeling, and is associated with pathways related to microtubule regulation, adipogenesis, and immune response regulation [1,2,3]. Genetic models, such as gene knockout mouse models, are valuable for studying its functions.

In T cells, Arl4d-deficient CD4 T cells show enhanced IL-2 secretion, more efficient conversion into Foxp3+ iTreg in vitro, and reduced colonic inflammation in a transfer colitis model, revealing its negative regulatory role in CD4 T-cell biology by restricting IL-2 production [4]. In adipogenesis, overexpression of Arl4D in 3T3-L1 cells inhibits differentiation and lipid accumulation, suggesting that a rapid reduction of Arl4D is required for adipogenesis to proceed [3].

In conclusion, Arl4d plays crucial roles in regulating cell-related processes like T-cell function and adipogenesis. Studies using Arl4d knockout mouse models have provided insights into its role in T-cell-mediated diseases and adipogenesis-related disorders, contributing to a better understanding of these biological processes and potential disease mechanisms.

References:

1. Lin, Shin-Jin, Huang, Chun-Fang, Wu, Tsung-Sheng, Li, Chun-Chun, Lee, Fang-Jen S. 2020. Arl4D-EB1 interaction promotes centrosomal recruitment of EB1 and microtubule growth. In Molecular biology of the cell, 31, 2348-2362. doi:10.1091/mbc.E18-10-0611. https://pubmed.ncbi.nlm.nih.gov/32755434/

2. Li, Chun-Chun, Chiang, Tsai-Chen, Wu, Tsung-Sheng, Moss, Joel, Lee, Fang-Jen S. 2007. ARL4D recruits cytohesin-2/ARNO to modulate actin remodeling. In Molecular biology of the cell, 18, 4420-37. doi:. https://pubmed.ncbi.nlm.nih.gov/17804820/

3. Yu, Jiahua, Ka, Sun-O, Kwon, Kang-Beom, Park, Jin-Woo, Park, Byung-Hyun. 2011. Overexpression of the small GTPase Arl4D suppresses adipogenesis. In International journal of molecular medicine, 28, 793-8. doi:10.3892/ijmm.2011.751. https://pubmed.ncbi.nlm.nih.gov/21769420/

4. Geers, Bernd, Hagenstein, Julia, Endig, Jessica, Tiegs, Gisa, Diehl, Linda. 2022. The ADP-Ribosylation Factor 4d Restricts Regulatory T-Cell Induction via Control of IL-2 Availability. In Cells, 11, . doi:10.3390/cells11172639. https://pubmed.ncbi.nlm.nih.gov/36078047/