RAB7A

Fig1. A schematic to present probable regulatory role of phosphorylation in Rab GTPase activity cycle. (Swapnil Rohidas Shinde, 2016)

What is RAB7A protein?

RAB7A (RAB7A, member RAS oncogene family) gene is a protein coding gene which situated on the long arm of chromosome 3 at locus 3q21. RAB family members are small, RAS-related GTP-binding proteins that are important regulators of vesicular transport. Each RAB protein targets multiple proteins that act in exocytic/endocytic pathways. This gene encodes a RAB family member that regulates vesicle traffic in the late endosomes and also from late endosomes to lysosomes. This encoded protein is also involved in the cellular vacuolation of the VacA cytotoxin of Helicobacter pylori. The RAB7A protein is consisted of 207 amino acids and its molecular mass is approximately 23.5 kDa.

What is the function of RAB7A protein?

RAB7A is a small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, it binds to a variety of effector proteins playing a key role in the regulation of endo-lysosomal trafficking. RAB7A governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. It plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transportor mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. RAB7A also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes.

RAB7A Related Signaling Pathway

The RAB7A protein is involved in several signaling pathways, the most important of which plays a key role in the endocytosomal lysosomal pathway. This protein regulates the maturation of endocytosomes and the incorporation of lysosomes, and promotes the activity of lysosomal enzymes, thus achieving intracellular waste degradation, phagocytosis of foreign substances and anti-microbial function. In addition, RAB7A is involved in the regulation of the autophagy process by regulating early and late steps in the autophagy pathway to promote self-recovery and clearance of damaged parts of the cell. In addition, there are cell cycle and proliferation, apoptosis, cell migration and invasion and other pathways.

RAB7A Related Diseases

Diseases associated with RAB7A include Charcot-Marie-Tooth disease, neurogranulocytosis, and congenital immune deficiency. These diseases are associated with abnormal or defective function of RAB7A protein, resulting in a lack of accurate endocytosis and lysosomal function within cells, affecting the normal function of several tissues and organs, including the nervous system and immune system. They also include cancer, neurodegenerative diseases and certain infectious diseases. For example, RAB7A is overexpressed in certain types of cancer, such as breast, prostate, and stomach cancers, and is associated with poorer prognosis. RAB7A is also involved in the endocytosis pathway of pathogens such as bacteria and viruses and may play a role in the host immune response.

Bioapplications of RAB7A

Because RAB7A has been linked to the onset and development of multiple diseases, particularly cancer, it is considered a potential drug target. Therefore, in the field of drug development, small molecule inhibitors or activators of RAB7A are being investigated to evaluate their potential value for disease treatment.

Case study 1: Huiyong Liu, 2020

Rab7 belongs to the Ras oncogene family. Many studies have shown that its dysfunction is associated with many types of malignant tumors, but its effect on the pathogenesis of gastric cancer (GC) is still unknown. Therefore, the researchers investigated the effect and mechanism of Rab7 in GC.

The expression of Rab7 in GC and adjacent tissues was detected by immunohistochemistry, Western blot analysis, and qRT-PCR. The relationship of Rab7 with clinicopathological parameters and prognosis was analyzed. The expressions of Rab7, PI3K, and AKT in GC cells were assessed by Western blot. Overexpressed and silenced GC cell lines were constructed and AGS cells were treated with LY294002. The expression of Rab7 was upregulated in the samples and cells, and was positively correlated with lymph node metastasis but negatively correlated with histological differentiation and clinical prognosis. In cell function experiments, overexpression of Rab7 induced the transition from S phase to G2 phase and promoted the proliferation, invasion, and migration of GC cells. These results show that the Rab7 affects GC cell progression by modulating the PI3K/AKT pathway.

Fig1. Rab7 promotes the proliferation, invasion and migration of GC cells through PI3K/AKT signaling pathway.

Fig2. Proliferation rate of GC cells after depleting or strengthening Rab7 expression, as determined by the CCK8 assay.

Case study 2: Guang Wang, 2019

The primary cilium is a sensory organelle that protrudes from the cell surface. Primary cilia undergo dynamic transitions between assembly and disassembly to exert their function in cell signaling. In this study, the researchers aimed to identify the function of small GTPase Rab7 in cilia disassembly.

By deleting the Rab7, they found it potently induced spontaneous ciliogenesis in proliferating cells and promoted cilia elongation during quiescence, knockdown of Rab7 blocked serum-induced ciliary resorption, and active Rab7 was required for this process. Mechanically, the failure of F-actin polymerization at the site of excision of cilia tips caused suppression of cilia ectocytosis on Rab7 depletion. Overall, the results suggest a novel function for Rab7 in regulating cilia ectocytosis and cilia disassembly via control of intraciliary F-actin polymerization.

Fig3. Rab7 knockdown promoted cilia elongation in quiescent (-serum) RPE-1 cells.

Fig4. Western analysis of Rab7 in RPE-1 cells after serum starvation and serum restimulation for the indicated times.

RAB7A 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 RAB7A itself. We selected most functions RAB7A had, and list some proteins which have the same functions with RAB7A. You can find most of the proteins on our site.

RAB7A 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 RAB7A here. Most of them are supplied by our site. Hope this information will be useful for your research of RAB7A.

RILP;1-phosphatidyl-1d-myo-inositol 3,5-bisphosphate;1-phosphatidyl-1d-myo-inositol 4,5-bisphosphate;DNM2;SH3KBP1;EIF1B;MCC;MPG;HLA-B;VHL;GABARAPL2;IKBKE;ATG5;PRKAB1;TRAF6