Rab8b-KO Mouse

Rab8b, a member of the Rab GTPase family, plays crucial roles in intracellular vesicle trafficking. It is involved in various pathways, such as the Wnt/β-catenin signaling pathway, and is important for maintaining normal cellular functions and organismal development [1]. Genetic models, like gene knockout mice, are valuable for studying its functions.

In a Wnt/β-catenin signaling RNAi screen, RAB8B was identified as essential. Depletion of RAB8B reduced LRP6 activity, β-catenin accumulation, and induction of Wnt target genes, while overexpression promoted LRP6 activity and internalization and rescued inhibition of caveolar endocytosis. In Xenopus laevis and Danio rerio, RAB8B morphants showed lower Wnt activity during embryonic development, indicating its conserved role in this signaling pathway [1]. RNAi analysis also revealed that Rab8b plays a role in the release of West Nile Virus (WNV) particles from recycling endosomes to the plasma membrane [2]. In AtT20 cells, Rab8b and its interacting partner TRIP8b are involved in the regulated secretory pathway, as both proteins stimulate cAMP-induced secretion of ACTH [3]. Generation of Rab8b-knockout mice showed that although they had no overt phenotype, Rab8a and Rab8b double-knockout mice exhibited mislocalization of apical markers, highlighting the compensatory effect of Rab8a and Rab8b in apical transport [4].

In summary, Rab8b is essential for multiple biological processes, including vesicle trafficking, signaling pathway regulation, and apical transport. Model-based research, especially the use of knockout mouse models, has provided significant insights into its functions. These findings have implications for understanding diseases related to disrupted vesicle trafficking and signaling, such as those associated with abnormal Wnt/β-catenin signaling [1,4].

References:

1. Demir, Kubilay, Kirsch, Nadine, Beretta, Carlo A, Niehrs, Christof, Boutros, Michael. 2013. RAB8B is required for activity and caveolar endocytosis of LRP6. In Cell reports, 4, 1224-34. doi:10.1016/j.celrep.2013.08.008. https://pubmed.ncbi.nlm.nih.gov/24035388/

2. Kobayashi, Shintaro, Suzuki, Tadaki, Kawaguchi, Akira, Orba, Yasuko, Sawa, Hirofumi. 2016. Rab8b Regulates Transport of West Nile Virus Particles from Recycling Endosomes. In The Journal of biological chemistry, 291, 6559-68. doi:10.1074/jbc.M115.712760. https://pubmed.ncbi.nlm.nih.gov/26817838/

3. Chen, S, Liang, M C, Chia, J N, Ngsee, J K, Ting, A E. 2001. Rab8b and its interacting partner TRIP8b are involved in regulated secretion in AtT20 cells. In The Journal of biological chemistry, 276, 13209-16. doi:. https://pubmed.ncbi.nlm.nih.gov/11278749/

4. Sato, Takashi, Iwano, Tomohiko, Kunii, Masataka, Harada, Reiko, Harada, Akihiro. 2013. Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis. In Journal of cell science, 127, 422-31. doi:10.1242/jcs.136903. https://pubmed.ncbi.nlm.nih.gov/24213529/