Rab5C, a member of the Rab GTPase family, is a crucial regulator of intracellular vesicular trafficking. It plays a significant role in the endocytic pathway, membrane protein recycling, and signaling, which are essential for normal cellular functions [1]. Genetic models, such as those in C. elegans and zebrafish, have been instrumental in studying its functions.

Missense variants in RAB5C have been associated with a neurodevelopmental disorder characterized by macrocephaly and mild-to-moderate developmental delay. In vitro and in vivo studies in C. elegans and zebrafish embryos showed that these variants disrupt the endocytic pathway [1]. In rectal cancer, Rab5C enhances resistance to ionizing radiation by modulating EGFR internalization and affecting DNA repair proteins [2]. In breast cancer cells, HuR promotes cell survival by facilitating RAB5C expression, and RAB5C functions as an oncogene [3]. In zebrafish embryos, Rab5c-mediated endocytic trafficking is essential for hematopoietic stem and progenitor cell development via Notch and AKT signaling [4].

In summary, Rab5C is vital for multiple biological processes, including endocytic trafficking, cell proliferation, and response to radiation. Research using various genetic models has revealed its role in neurodevelopmental disorders, cancer, and hematopoietic development, providing insights into potential therapeutic targets for related diseases.

References:

1. Koop, Klaas, Yuan, Weimin, Tessadori, Federico, Schedl, Tim, van Hasselt, Peter. . Macrocephaly and developmental delay caused by missense variants in RAB5C. In Human molecular genetics, 32, 3063-3077. doi:10.1093/hmg/ddad130. https://pubmed.ncbi.nlm.nih.gov/37552066/

2. Baptistella, Antuani Rafael, Landemberger, Michele Christine, Dias, Marcos Vinicios Salles, Aguiar, Samuel, Martins, Vilma Regina. 2019. Rab5C enhances resistance to ionizing radiation in rectal cancer. In Journal of molecular medicine (Berlin, Germany), 97, 855-869. doi:10.1007/s00109-019-01760-6. https://pubmed.ncbi.nlm.nih.gov/30968159/

3. Wang, Zhenzhen, Li, Fang, Zhang, Huahua, Chen, Yanke, Huang, Chen. 2022. RAB5C, a new mRNA binding target of HuR, regulates breast cancer cell proliferation. In Cell biology international, 47, 374-382. doi:10.1002/cbin.11969. https://pubmed.ncbi.nlm.nih.gov/36480789/

4. Heng, Jian, Lv, Peng, Zhang, Yifan, Ma, Dongyuan, Liu, Feng. 2020. Rab5c-mediated endocytic trafficking regulates hematopoietic stem and progenitor cell development via Notch and AKT signaling. In PLoS biology, 18, e3000696. doi:10.1371/journal.pbio.3000696. https://pubmed.ncbi.nlm.nih.gov/32275659/