Zhang Xinjun's team from the School of Life, Huazhong University of Science and Technology discovered that the small G protein RAB21 regulates autophagy and energy homeostasis

On August 21, 2022, the team of Professor Zhang Xinjun from the School of Life Science and Technology of Huazhong University of Science and Technology published the latest research results online entitled "RAB21 controls autophagy and cellular energy homeostasis by regulating retromer-mediated recycling of SLC2A1/GLUT1" in "Autophagy" magazine.

The cellular endosome transport system maintains cellular homeostasis by coordinating multiple intracellular vesicle transport processes to achieve material exchange and information transfer between organelles

The RAB protein family is the largest branch of the Ras-like small G protein family, and more than 60 species have been reported

First, the study found that knockout of RAB21 resulted in a significant increase in autophagic flux and a significant increase in the efficiency of autophagosome clearance (fusion with lysosomes)

Figure 1: RAB21 knockout cells increased autophagic flux, increased apoptosis rate under starvation conditions, activated AMPK pathway, and increased ULK1 protein level and phosphorylation

The AMPK pathway is a central hub for maintaining cellular energy homeostasis, and it is particularly sensitive to glucose among many nutrients, so the authors speculated whether RAB21-knockout cells were suffering from nutrient (especially glucose) deprivation

Through further research, the authors found that in RAB21 knockout cells, the retromer complex responsible for reverse transport, the WASH complex, and the sorting protein SNX27 responsible for sorting cell membrane receptors are all retained on early endosomes, and RAB21 knockout The morphological changes of early endosomes in excepted cells were markedly increased, showing increased volume and a distinct tubular structure

Figure 2: The reverse transport of SLC2A1 in RAB21 knockout cells is blocked, the level of SLC2A1 on the cell membrane surface is reduced, the efficiency of glucose uptake by cells is reduced, and the morphology of early endosomes is changed

Finally, through tumor cell xenograft experiments, the authors found that the tumorigenic rate and tumor volume and mass of RAB21-knockout cells were significantly lower than those of wild-type cells, which made RAB21 a potential target for tumor therapy after SLC2A1

Full text summary: In wild-type cells, the retromer complex mediates the retrograde transport of cell membrane receptors (such as SLC2A1, etc.

Figure 3: RAB21 is involved in retromer-mediated reverse trafficking of cell membrane receptors

Pei Yifei and Lu Shuning, Ph.

Paper link: https://doi.