RAB10

What is RAB10 protein?

RAB10 (RAB10, member RAS oncogene family) gene is a protein coding gene which situated on the short arm of chromosome 2 at locus 2p23. RAB10 is a member of the Ras-related small GTPase (Rab GTPases) family, which are molecular switches that play crucial roles in regulating various cellular processes, particularly in vesicular trafficking and membrane transport. Rab proteins cycle between an active GTP-bound state and an inactive GDP-bound state, which allows them to interact with a range of effector proteins and facilitate the movement of vesicles within cells. The RAB10 protein is consisted of 200 amino acids and its molecular mass is approximately 22.5 kDa.

What is the function of RAB10 protein?

RAB10, specifically, has been implicated in the regulation of polarized sorting and recycling transport, particularly in epithelial cells. It is involved in the transport process from early endosomes to recycling endosomes, and its activity is critical for the proper functioning of cells. When RAB10 functions abnormally, it can lead to the mislocalization of various subcellular structures, which can result in physiological deformities and diseases such as immunodeficiency, cancer, and neurological disorders.

Fig1. Multiple pathways of LRRK2-Rab10 interaction in dopaminergic neurons. (Alison Fellgett, 2021)

RAB10 Related Signaling Pathway

RAB10 is involved in the regulation of endosomal trafficking, particularly in the transport from early endosomes to recycling endosomes. It helps in the sorting and recycling of membrane proteins and lipids, which is crucial for maintaining cellular homeostasis. RAB10 may also be involved in the trafficking of G protein-coupled receptors (GPCRs), which are important drug targets for a wide range of conditions. RAB10 may play a role in cell adhesion and migration, which are critical for processes like wound healing and tissue regeneration. There is also a potential link between RAB10 and autophagy, a cellular process for the degradation and recycling of cellular components, which can be important for maintaining cellular health and responding to stress.

RAB10 Related Diseases

The role of RAB10 has been explored in the context of different diseases. For instance, it has been associated with Carpenter Syndrome (type 1) and Microvillus Inclusion Disease, as mentioned in GeneCards. Additionally, RAB10 has been studied for its potential involvement in Alzheimer's disease, where it is considered a resilience locus and a potential drug target. It has also been linked to the susceptibility to Parkinson's disease, Crohn's disease, and mycobacteria infection, as well as playing a role in the coordination of macropinocytosis. Furthermore, RAB10's expression can be induced by lipopolysaccharide (LPS), and blockade of RAB10 function can lead to decreased membrane TLR4 expression and diminished production of inflammatory cytokines, suggesting a role in inflammatory responses.

Bioapplications of RAB10

RAB10 is involved in the progression of various malignancies, including liver cancer, cervical cancer, and glioma. It may be involved in cancer cell proliferation, migration, and invasion, making it a potential therapeutic target for cancer treatment. Studies have shown that RAB10's expression levels are associated with the prognosis of breast cancer (BC), and it may promote BC cell proliferation and invasion in vitro, indicating its potential as a biomarker or molecular target for BC.

Case Study 1: Jian Zhuo, 2023

RAB10, a member of the small GTPase family, has complex biological functions, but its role in breast cancer (BC) remains unclear. The aim of this study was to investigate the relationship between RAB10's role in BC, its biological functions, and BC prognosis. An online database was used to analyze the correlation between differential expression of RAB10 in BC and prognosis. The results of immunohistochemical assays in clinical cohorts were combined with the database analysis. The chi-square test and COX regression were employed to analyze the correlation between RAB10 and pathological features of BC. MTT, Transwell, and wound healing assays were conducted to detect BC cell proliferation, invasion, and metastatic ability. Bioinformatics techniques were employed to explore the correlation between RAB10 and BC tumor immune cell infiltration, and to speculate the biological function of RAB10 in BC and related signaling pathways. These findings suggest that RAB10 expression is elevated in BC and is associated with HER2 status, indicating a poor prognosis for BC patients. RAB10 can promote the proliferation, migration, and invasion ability of BC cells in vitro. RAB10 is also associated with BC immune cell infiltration and interacts with multiple signaling pathways. RAB10 is a potential biomarker or molecular target for BC.

Fig1. The UALCAN database shows a significant upregulation of RAB10 protein in BC.

Fig2. RAB10-shRNA infection of HCC1937 and MDA-MB-231 cells was detected using western blotting.

Case Study 2: Wei Wang, 2017

Hepatocellular carcinoma (HCC), one of the most common and lethal cancers worldwide, has a high recurrence rate with current treatment modalities. Identifying biomarkers for early diagnosis and discovering new sufficient molecular targets for the development of targeted therapies are urgently needed. RAB10, a member of the RAS family, has been shown to be highly expressed in HCC. However, the function of RAB10 in HCC is less studied. Here the researchers report that RAB10 acts as an oncogene in HCC. The shRNA-mediated knockdown of RAB10 significantly reduced the proliferation of HCC cells and colony formation, induced cell cycle arrest at G0/G1 phase and increased apoptosis in vitro. In addition, RAB10 knockdown suppressed HCC growth in nude mice. Moreover, RAB10 silencing decreased the phosphorylation of InsR, Met/HGFR, Ron/MST1R, Ret, c-Kit/SCFR, EphA3, EphB4, Tyro3/Dtk, Axl, Tie2/TEK, VEGFR2/KDR, Akt/PKB/Rac, S6 Ribosomal Protein and c-Abl, while the phosphorylation of HSP27, p38 MAPK, Chk2 and TAK1 increased significantly. These results suggest that RAB10 regulates cell survival and proliferation through multiple oncogenic, cell stress and apoptosis pathways. More importantly, high RAB10 expression levels in HCC cells correlated with a poor prognosis in HCC patients.

Fig3. RAB10 protein levels in SMMC-7721 cells.

Fig4. Protein levels of select genes in SMMC-7721 cells transfected with negative control shRNA (NC) or RAB10 shRNA (KD) measured by Western blot.

RAB10 has several biochemical functions, for example, GDP binding,GTP binding,GTPase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by RAB10 itself. We selected most functions RAB10 had, and list some proteins which have the same functions with RAB10. You can find most of the proteins on our site.

RAB10 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with RAB10 here. Most of them are supplied by our site. Hope this information will be useful for your research of RAB10.

OPTN;ganglioside_gm1;7242199;AURKA;DOK2;EPB41;RAB8A;AP1S1;MFSD1;TRAF6;q5nfa1_fratt;MICALL1;SBBI23;ENOPH1;UL36;pi3p;1-phosphatidyl-1d-myo-inositol 4,5-bisphosphate