Rab10-KO Mouse

Rab10, a member of the small GTPase family, is involved in multiple cellular functions such as vesicle transport and endosomal regulation [1,6]. It participates in pathways related to cell migration, lysosomal function, and neurodegeneration, thus being of great biological importance. Genetic models like Rab10 knockout mice are valuable tools for studying its functions.

In a study of Rab10+/- mice, they showed increased activation of pathways related to neuronal metabolism, structural integrity, etc., and lower activation in neuroinflammation-associated pathways. Behaviorally, these mice performed better in a hippocampal-dependent spatial task but were impaired in a classical conditioning task, indicating Rab10's differential control over brain circuitry [7]. In hepatocellular carcinoma, O-GlcNAcylation of RAB10 by OGT was found to stabilize RAB10 and accelerate cancer progression [2]. Also, Rab10 and CAV1 mark the intraluminal vesicles in migrasomes, and the transport of Rab10-CAV1 vesicles to migrasomes is regulated by LRRK2-mediated phosphorylation of Rab10, which has implications in monocyte-macrophage differentiation during skin wound healing [1]. In Parkinson's disease-related research, lysosomal positioning was shown to regulate Rab10 phosphorylation by LRRK2 [3], and VPS13C was found to regulate phospho-Rab10-mediated lysosomal function in human dopaminergic neurons [4]. Additionally, urinary Rab10 phosphorylation was elevated in idiopathic Parkinson disease and associated with disease progression [5]. In breast cancer, RAB10 expression is elevated, promoting cell proliferation, migration, and invasion, and is associated with a poor prognosis [8].

In conclusion, Rab10 plays essential roles in diverse biological processes and disease conditions. Studies using mouse models, especially Rab10+/- mice, have provided insights into its functions in the context of neurodegenerative diseases like Alzheimer's and Parkinson's, as well as in cancer development. These findings contribute to understanding the underlying mechanisms of these diseases and potentially identifying novel therapeutic targets.

References:

1. Li, Yong, Wen, Yiling, Li, Ying, Wong, Catherine C L, Chen, Yang. 2024. Rab10-CAV1 mediated intraluminal vesicle transport to migrasomes. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2319267121. doi:10.1073/pnas.2319267121. https://pubmed.ncbi.nlm.nih.gov/39008679/

2. Lv, Zhuo, Ma, Guolu, Zhong, Zhuo, Li, Bin, Long, De. . O-GlcNAcylation of RAB10 promotes hepatocellular carcinoma progression. In Carcinogenesis, 44, 785-794. doi:10.1093/carcin/bgad034. https://pubmed.ncbi.nlm.nih.gov/37218374/

3. Kluss, Jillian H, Beilina, Alexandra, Williamson, Chad D, Cookson, Mark R, Bonet-Ponce, Luis. 2022. Lysosomal positioning regulates Rab10 phosphorylation at LRRK2+ lysosomes. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2205492119. doi:10.1073/pnas.2205492119. https://pubmed.ncbi.nlm.nih.gov/36256825/

4. Schrӧder, Leonie F, Peng, Wesley, Gao, Ge, Schwake, Michael, Krainc, Dimitri. 2024. VPS13C regulates phospho-Rab10-mediated lysosomal function in human dopaminergic neurons. In The Journal of cell biology, 223, . doi:10.1083/jcb.202304042. https://pubmed.ncbi.nlm.nih.gov/38358348/

5. Wang, Shijie, Unnithan, Shakthi, Bryant, Nicole, Al-Khalidi, Hussein R, West, Andrew B. 2022. Elevated Urinary Rab10 Phosphorylation in Idiopathic Parkinson Disease. In Movement disorders : official journal of the Movement Disorder Society, 37, 1454-1464. doi:10.1002/mds.29043. https://pubmed.ncbi.nlm.nih.gov/35521944/

6. Etoh, Kan, Fukuda, Mitsunori. 2019. Rab10 regulates tubular endosome formation through KIF13A and KIF13B motors. In Journal of cell science, 132, . doi:10.1242/jcs.226977. https://pubmed.ncbi.nlm.nih.gov/30700496/

7. Bunner, Wyatt, Wang, Jie, Cohen, Sarah, Yasuda, Ryohei, Szatmari, Erzsebet M. 2023. Behavioral and Transcriptome Profiling of Heterozygous Rab10 Knock-Out Mice. In eNeuro, 10, . doi:10.1523/ENEURO.0459-22.2023. https://pubmed.ncbi.nlm.nih.gov/37156612/

8. Zhuo, Jian, Han, Jianjun, Zhao, Yanchun, Yang, Xiaohong, Liu, Weiguang. 2023. RAB10 promotes breast cancer proliferation migration and invasion predicting a poor prognosis for breast cancer. In Scientific reports, 13, 15252. doi:10.1038/s41598-023-42434-1. https://pubmed.ncbi.nlm.nih.gov/37709911/