Rab27b, a member of the Rab family of GTPases, is involved in multiple cellular processes such as endocytosis, exocytosis, and vesicle trafficking [6]. It also plays a role in exosome secretion, which is crucial for intercellular communication [2,3,4,5,7,10]. Dysregulation of Rab27b is associated with various diseases, highlighting its biological importance [1,3,4,5,6,7,8,10]. Genetic models, like knockout (KO) mouse models, have been instrumental in studying Rab27b's functions.

In KO mouse models, Rab27b deficiency abrogated mutant but not WT NRAS-mediated progenitor cell growth, ERK signaling, and NRAS palmitoylation, and significantly reduced myelomonocytic leukemia development in vivo. This indicates that Rab27b controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia [1]. In another context, Rab27b knockout led to distinct functional changes at different hippocampal synapses, such as reduced frequency facilitation at the DG/MF-CA3 synaptic region and increased facilitation at the SC-CA1 synaptic region, and a complete elimination of LTP at the MF-CA3 synapse [9].

In summary, Rab27b is essential for vesicle-related functions and exosome secretion. KO mouse models have revealed its role in myeloid leukemia development and synaptic transmission. Understanding Rab27b's functions through model-based research provides insights into the mechanisms of related diseases and potential therapeutic targets.

References:

1. Ren, Jian-Gang, Xing, Bowen, Lv, Kaosheng, Philips, Mark R, Tong, Wei. 2023. RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia. In The Journal of clinical investigation, 133, . doi:10.1172/JCI165510. https://pubmed.ncbi.nlm.nih.gov/37317963/

2. Ostrowski, Matias, Carmo, Nuno B, Krumeich, Sophie, Moita, Luis F, Thery, Clotilde. 2009. Rab27a and Rab27b control different steps of the exosome secretion pathway. In Nature cell biology, 12, 19-30; sup pp 1-13. doi:10.1038/ncb2000. https://pubmed.ncbi.nlm.nih.gov/19966785/

3. Shan, Jing, Chang, Ling-Yu, Li, Da-Jin, Wang, Xiao-Qiu. . Rab27b promotes endometriosis by enhancing invasiveness of ESCs and promoting angiogenesis. In American journal of reproductive immunology (New York, N.Y. : 1989), 90, e13762. doi:10.1111/aji.13762. https://pubmed.ncbi.nlm.nih.gov/37641372/

4. Yang, Jingxuan, Zhang, Zicheng, Zhang, Yuqing, Li, Yi-Ping, Li, Min. 2018. ZIP4 Promotes Muscle Wasting and Cachexia in Mice With Orthotopic Pancreatic Tumors by Stimulating RAB27B-Regulated Release of Extracellular Vesicles From Cancer Cells. In Gastroenterology, 156, 722-734.e6. doi:10.1053/j.gastro.2018.10.026. https://pubmed.ncbi.nlm.nih.gov/30342032/

5. Chen, Ying, Wen, Jin, Li, Qian, Li, Lei, Liu, Lingbo. 2023. RAB27B-regulated exosomes mediate LSC maintenance via resistance to senescence and crosstalk with the microenvironment. In Leukemia, 38, 266-280. doi:10.1038/s41375-023-02097-3. https://pubmed.ncbi.nlm.nih.gov/38036630/

6. Meng, Can, Huang, Li, Fu, Xiangjun, Wu, Bin, Lin, Lie. . RAB27B inhibits proliferation and promotes apoptosis of leukemic cells via 3-Hydroxy butyrate dehydrogenase 2 (BDH2). In Bioengineered, 13, 5103-5112. doi:10.1080/21655979.2022.2036903. https://pubmed.ncbi.nlm.nih.gov/35164665/

7. Meneses, Kayleah M, Pandya, Prita, Lindemann, Jennifer A, Patel, Tushar, Justilien, Verline. 2023. RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion. In Cancer research communications, 3, 607-620. doi:10.1158/2767-9764.CRC-22-0425. https://pubmed.ncbi.nlm.nih.gov/37077938/

8. Pecqueux, Mathieu, Wende, Beate, Sommer, Ulrich, Weitz, Jürgen, Kahlert, Christoph. . RAB27B expression in pancreatic cancer is predictive of poor survival but good response to chemotherapy. In Cancer biomarkers : section A of Disease markers, 37, 207-215. doi:10.3233/CBM-220460. https://pubmed.ncbi.nlm.nih.gov/37248891/

9. Arias-Hervert, Erwin R, Xu, Nicole, Njus, Meredith, Ernst, Stephen A, Stuenkel, Edward L. . Actions of Rab27B-GTPase on mammalian central excitatory synaptic transmission. In Physiological reports, 8, e14428. doi:10.14814/phy2.14428. https://pubmed.ncbi.nlm.nih.gov/32358861/

10. Nambara, Sho, Masuda, Takaaki, Hirose, Kosuke, Yoshizumi, Tomoharu, Mimori, Koshi. . Rab27b, a Regulator of Exosome Secretion, Is Associated With Peritoneal Metastases in Gastric Cancer. In Cancer genomics & proteomics, 20, 30-39. doi:10.21873/cgp.20362. https://pubmed.ncbi.nlm.nih.gov/36581340/