Rab5b, a small monomeric G protein, is a key regulator of early endocytosis [3]. It controls signaling pathways related to cell growth, survival, and apoptosis. Dysregulation of its expression has been associated with the development of multiple cancers such as leukemia, lymphoma, and various solid tumors [3]. Genetic models, like gene knockout (KO) in mice or other organisms, can be valuable for studying its functions.

In pancreatic ductal adenocarcinoma (PDAC) with KRAS mutations, the Rab5B-CD109 interplay bypasses traditional endosomal trafficking. This promotes axonogenesis and perineural invasion (PNI) through a series of molecular events involving EV-packaged circRNAs [1]. In Leishmania, Rab5b null-mutants showed a severe growth defect and inability to internalize hemoglobin, indicating its essential role in acquiring heme from hemoglobin endocytosis for survival [2]. A dominant-negative variant of RAB5B in a child with interstitial lung disease disrupted the maturation of surfactant protein B and surfactant protein C, suggesting its role in the surfactant secretion pathway [4].

In summary, Rab5b is crucial for endocytosis-related functions, including heme acquisition in Leishmania and surfactant protein maturation in the lung. In PDAC, it is involved in promoting PNI. The use of KO or other loss-of-function models has revealed these important roles of Rab5b in specific biological processes and disease conditions, providing insights into potential therapeutic targets for diseases such as neuro-metastatic PDAC and surfactant-related lung diseases.

References:

1. Zhang, Dingwen, Luo, Yuming, Lin, Yan, Chen, Changhao, Chen, Rufu. 2024. Endosomal Trafficking Bypassed by the RAB5B-CD109 Interplay Promotes Axonogenesis in KRAS-Mutant Pancreatic Cancer. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2405092. doi:10.1002/advs.202405092. https://pubmed.ncbi.nlm.nih.gov/39488792/

2. Rastogi, Ruchir, Kapoor, Anjali, Verma, Jitender Kumar, Kumar, Kamal, Mukhopadhyay, Amitabha. 2020. Rab5b function is essential to acquire heme from hemoglobin endocytosis for survival of Leishmania. In Biochimica et biophysica acta. Molecular cell research, 1868, 118868. doi:10.1016/j.bbamcr.2020.118868. https://pubmed.ncbi.nlm.nih.gov/33011192/

3. Kashyap, Dharmendra, Koirala, Suman, Saini, Vaishali, Kar, Parimal, Jha, Hem Chandra. 2023. Prediction of Rab5B inhibitors through integrative in silico techniques. In Molecular diversity, 28, 2547-2562. doi:10.1007/s11030-023-10693-9. https://pubmed.ncbi.nlm.nih.gov/37505376/

4. Huang, Huiyan, Pan, Jiehong, Spielberg, David R, Brody, Steven L, Schedl, Tim. . A dominant negative variant of RAB5B disrupts maturation of surfactant protein B and surfactant protein C. In Proceedings of the National Academy of Sciences of the United States of America, 119, . doi:10.1073/pnas.2105228119. https://pubmed.ncbi.nlm.nih.gov/35121658/