Rab37, a member of the RAS oncogene family, is a small GTPase that plays a crucial role in vesicle biogenesis, trafficking, and cargo release [1,3,8,10]. It is involved in various biological processes, including autophagy, insulin secretion, and cell differentiation. The regulation of Rab37 is associated with multiple signaling pathways, such as those involving transcription factors EBF1, E2F1, and EGR2 [2]. Genetic models, especially KO/CKO mouse models, have been instrumental in understanding its functions.

Conditional knockout of Rab37 in oocytes impairs autophagy in the ovary, disrupting follicular homeostasis and ovarian development in mice, highlighting its role in maintaining ovarian function [1]. In pancreatic β -cells, the active form of Rab37 is essential for autophagy-promoted insulin secretion, as this is not observed in rab37 knockout cells and mice [3]. In adipose-derived mesenchymal stem cells (ADSCs), Rab37 promotes endothelial differentiation and accelerates diabetic wound healing, and in human ADSCs, it positively regulates adipogenic differentiation [4,5]. In lung cancer, Rab37 is involved in multiple processes. It mediates the trafficking and membrane presentation of ST2L in M2 macrophages and PD-1 in T cells, contributing to tumor progression, and also regulates IL-6 secretion in macrophages to trigger M2 polarization [6,7,9].

In conclusion, Rab37 is a key regulator in multiple biological processes. Studies using KO/CKO mouse models have significantly enhanced our understanding of its functions in ovarian homeostasis, insulin secretion, cell differentiation, and cancer-related immune regulation. These findings provide insights into potential therapeutic targets for diseases related to these processes, such as ovarian dysfunction, metabolic diseases, and lung cancer.

References:

1. Xu, Xu, Hu, Mengxin, Ying, Ruhong, Cheng, Hanhua, Zhou, Rongjia. 2024. RAB37-mediated autophagy guards ovarian homeostasis and function. In Autophagy, 20, 2738-2751. doi:10.1080/15548627.2024.2389568. https://pubmed.ncbi.nlm.nih.gov/39113565/

2. Xu, Xu, Hu, Mengxin, Ying, Ruhong, Cheng, Hanhua, Zhou, Rongjia. 2020. RAB37 multiple alleles, transcription activation and evolution in mammals. In International journal of biological sciences, 16, 2964-2973. doi:10.7150/ijbs.47959. https://pubmed.ncbi.nlm.nih.gov/33061809/

3. Wu, Shan-Ying, Wu, Hung-Tsung, Wang, Yi-Ching, Lan, Sheng-Hui, Liu, Hsiao-Sheng. 2022. Secretory autophagy promotes RAB37-mediated insulin secretion under glucose stimulation both in vitro and in vivo. In Autophagy, 19, 1239-1257. doi:10.1080/15548627.2022.2123098. https://pubmed.ncbi.nlm.nih.gov/36109708/

4. Huang, Haili, Liang, Ling, Sun, Dan, Tang, Xudong, Zhang, Peihua. 2023. Rab37 Promotes Endothelial Differentiation and Accelerates ADSC-Mediated Diabetic Wound Healing through Regulating Secretion of Hsp90α and TIMP1. In Stem cell reviews and reports, 19, 1019-1033. doi:10.1007/s12015-022-10491-0. https://pubmed.ncbi.nlm.nih.gov/36627432/

5. Huang, Haili, Li, Anran, Li, Jin, He, Chengzhang, Zhang, Peihua. 2021. RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway. In Stem cells international, 2021, 8297063. doi:10.1155/2021/8297063. https://pubmed.ncbi.nlm.nih.gov/34858503/

6. Yang, You-En, Hu, Meng-Hsuan, Zeng, Yen-Chen, Chang, Chih-Peng, Wang, Yi-Ching. 2024. IL-33/NF-κB/ST2L/Rab37 positive-feedback loop promotes M2 macrophage to limit chemotherapeutic efficacy in lung cancer. In Cell death & disease, 15, 356. doi:10.1038/s41419-024-06746-y. https://pubmed.ncbi.nlm.nih.gov/38778059/

7. Kuo, Wan-Ting, Kuo, I-Ying, Hsieh, Hung-Chia, Su, Wu-Chou, Wang, Yi-Ching. 2024. Rab37 mediates trafficking and membrane presentation of PD-1 to sustain T cell exhaustion in lung cancer. In Journal of biomedical science, 31, 20. doi:10.1186/s12929-024-01009-6. https://pubmed.ncbi.nlm.nih.gov/38321486/

8. Wu, Shan-Ying, Chen, Jia-Wen, Liu, Hsi-Yu, Liu, Hsiao-Sheng, Lan, Sheng-Hui. 2022. Secretory autophagy promotes Rab37-mediated exocytosis of tissue inhibitor of metalloproteinase 1. In Journal of biomedical science, 29, 103. doi:10.1186/s12929-022-00886-z. https://pubmed.ncbi.nlm.nih.gov/36457117/

9. Kuo, I-Ying, Yang, You-En, Yang, Pei-Shan, Chang, Chih-Peng, Wang, Yi-Ching. 2021. Converged Rab37/IL-6 trafficking and STAT3/PD-1 transcription axes elicit an immunosuppressive lung tumor microenvironment. In Theranostics, 11, 7029-7044. doi:10.7150/thno.60040. https://pubmed.ncbi.nlm.nih.gov/34093869/

10. Wu, Shan-Ying, Wang, Yi-Ching, Zuchini, Roberto, Liu, Hsiao-Sheng, Lan, Sheng-Hui. 2023. Secretory autophagy-promoted cargo exocytosis requires active RAB37. In Autophagy, 20, 933-934. doi:10.1080/15548627.2023.2210446. https://pubmed.ncbi.nlm.nih.gov/37151129/