Rab33b-KO Mouse

Rab33b, a member of the RAS oncogene family, localizes to the Golgi apparatus. It functions in both membrane trafficking and autophagic processes, with a significant role in maintaining cellular homeostasis [4]. In membrane trafficking, it has been shown to regulate Golgi-to-ER retrograde trafficking, Golgi homeostasis, and post-Golgi transport to the plasma membrane [1]. In autophagy, it is involved in autophagosome formation [2,3].

A Rab33b missense mouse model for Smith-McCort dysplasia (SMC) showed bone resorption defects and altered protein glycosylation. The mutation in male mice led to changes in trabecular and cortical bone thickness, suggesting a role of Rab33b in osteoclast function [5]. RNA interference-based studies in hepatoma cell lines indicated that Rab33B is required for hepatitis B virus (HBV) propagation, guiding core transport to NC assembly and budding sites [6].

In conclusion, Rab33b is crucial for membrane trafficking and autophagy. The Rab33b missense mouse model has revealed its role in SMC-related bone resorption defects, and in vitro studies have shown its importance in HBV propagation. These findings contribute to understanding the molecular mechanisms of these biological processes and diseases related to Rab33b dysfunction.

References:

1. Bjørnestad, Synne Arstad, Guadagno, Noemi Antonella, Kjos, Ingrid, Progida, Cinzia. 2022. Rab33b-exocyst interaction mediates localized secretion for focal adhesion turnover and cell migration. In iScience, 25, 104250. doi:10.1016/j.isci.2022.104250. https://pubmed.ncbi.nlm.nih.gov/35521520/

2. Pantoom, Supansa, Konstantinidis, Georgios, Voss, Stephanie, Li, Zhiyu, Wu, Yao-Wen. 2020. RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein. In Autophagy, 17, 2290-2304. doi:10.1080/15548627.2020.1822629. https://pubmed.ncbi.nlm.nih.gov/32960676/

3. Metje-Sprink, Janina, Groffmann, Johannes, Neumann, Piotr, Schalk, Amanda M, Binotti, Beyenech. 2020. Crystal structure of the Rab33B/Atg16L1 effector complex. In Scientific reports, 10, 12956. doi:10.1038/s41598-020-69637-0. https://pubmed.ncbi.nlm.nih.gov/32737358/

4. Morgan, Niamh E, Cutrona, Meritxell B, Simpson, Jeremy C. 2019. Multitasking Rab Proteins in Autophagy and Membrane Trafficking: A Focus on Rab33b. In International journal of molecular sciences, 20, . doi:10.3390/ijms20163916. https://pubmed.ncbi.nlm.nih.gov/31408960/

5. Dimori, Milena, Pokrovskaya, Irina D, Liu, Shijie, Lupashin, Vladimir V, Morello, Roy. 2023. A Rab33b missense mouse model for Smith-McCort dysplasia shows bone resorption defects and altered protein glycosylation. In Frontiers in genetics, 14, 1204296. doi:10.3389/fgene.2023.1204296. https://pubmed.ncbi.nlm.nih.gov/37359363/

6. Bartusch, Christina, Döring, Tatjana, Prange, Reinhild. 2017. Rab33B Controls Hepatitis B Virus Assembly by Regulating Core Membrane Association and Nucleocapsid Processing. In Viruses, 9, . doi:10.3390/v9060157. https://pubmed.ncbi.nlm.nih.gov/28635671/