Rab19-KO Mouse

Rab19, a small GTPase of the Rab subfamily, is tissue-specifically expressed, with high levels in intestine, lung, and spleen, and lower levels in kidney [5]. It is involved in multiple biological processes. Notably, it plays a crucial role in primary ciliogenesis, coordinating cortical remodeling and membrane growth, which is essential for the formation of these sensory organelles [1]. Additionally, it is associated with endolysosomal cargo trafficking and acrosome biogenesis [2,3,4].

In polarized epithelial cells, Rab19-mediated clearing of apical cortical actin is required for ciliogenesis. Loss of the lysosomal membrane-tethering HOPS complex disrupts the targeting of Rab19 to the basal body, impairing actin-clearing and ciliogenesis [2,3]. In non-polarized cell types, Rab19 loss blocks ciliogenesis even with a docked ciliary vesicle [1]. In Drosophila, loss of Rab19 impairs Slit production in the gut, disrupting the differentiation of pre-enteroendocrine cells and triggering an intestinal inflammatory response, potentially related to the development of inflammatory bowel disease [6].

In summary, Rab19 is essential for primary ciliogenesis, endolysosomal cargo trafficking, and acrosome biogenesis. Studies, especially those using loss-of-function models like in Drosophila, have revealed its significance in processes relevant to ciliogenesis and disease-related pathways such as those associated with inflammatory bowel disease. These findings contribute to our understanding of biological functions and disease mechanisms related to Rab19.

References:

1. Jewett, Cayla E, Soh, Adam W J, Lin, Carrie H, Pearson, Chad G, Prekeris, Rytis. . RAB19 Directs Cortical Remodeling and Membrane Growth for Primary Ciliogenesis. In Developmental cell, 56, 325-340.e8. doi:10.1016/j.devcel.2020.12.003. https://pubmed.ncbi.nlm.nih.gov/33561422/

2. Hoffman, Huxley K, Prekeris, Rytis. 2023. HOPS-dependent lysosomal fusion controls Rab19 availability for ciliogenesis in polarized epithelial cells. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.02.07.527563. https://pubmed.ncbi.nlm.nih.gov/36798155/

3. Hoffman, Huxley K, Prekeris, Rytis. 2023. HOPS-dependent lysosomal fusion controls Rab19 availability for ciliogenesis in polarized epithelial cells. In Journal of cell science, 137, . doi:10.1242/jcs.261047. https://pubmed.ncbi.nlm.nih.gov/37665101/

4. Gao, Qiujie, Liu, Gang, Huang, Lihua, Song, Xiaoyue, Xing, Xiaowei. . WDR38, a novel equatorial segment protein, interacts with the GTPase protein RAB19 and Golgi protein GM130 to play roles in acrosome biogenesis. In Acta biochimica et biophysica Sinica, 55, 1561-1570. doi:10.3724/abbs.2023126. https://pubmed.ncbi.nlm.nih.gov/37635409/

5. Lütcke, A, Olkkonen, V M, Dupree, P, Simons, K, Zerial, M. . Isolation of a murine cDNA clone encoding Rab19, a novel tissue-specific small GTPase. In Gene, 155, 257-60. doi:. https://pubmed.ncbi.nlm.nih.gov/7721101/

6. Nagy, Péter, Szatmári, Zsuzsanna, Sándor, Gyöngyvér O, Hegedűs, Krisztina, Juhász, Gábor. 2017. Drosophila Atg16 promotes enteroendocrine cell differentiation via regulation of intestinal Slit/Robo signaling. In Development (Cambridge, England), 144, 3990-4001. doi:10.1242/dev.147033. https://pubmed.ncbi.nlm.nih.gov/28982685/