ArfGAP3 regulates vesicle transport and glucose uptake in myoblasts

Abstract

Skeletal muscle injuries are common, and damaged myofibers are repaired through proliferation and differentiation of muscle satellite cells. GLUT4 is enriched in GLUT4 storage vesicles (GSVs) and plays a crucial role in the maintenance of muscle function. ArfGAP3 regulates the vesicle transport especially for COPI coat assembly, but its effects on GSVs and the repair process after skeletal muscle injury remains unclear. In this study, datasets related to skeletal muscle injury and myoblast differentiation GSE469, GSE5413, GSE45577 and GSE108040 were retrieved through the GEO database and the expression of heptameric coat protein complex I (COPI) and Golgi vesicle transport-related genes in various datasets, as well as the expression correlation between ArfGAP2, ArfGAP3 and COPI-related genes COPA, COPB1, COPB2, COPE, COPZ1, COPZ2 were analyzed. The results suggested that ArfGAP3 was expressed in the process of repair after skeletal muscle injury and myoblast differentiation and that ArfGAP3 was positively correlated with COPI-related genes. In vitro experimental results showed that ArfGAP3 was colocalized with COPA, COPB, COPG protein, and GLUT4 in C2C12 myoblasts. After the downregulation of ArfGAP3 expression, intracellular vesicle transport, and glucose uptake were blocked, the proliferation of myoblasts under low glucose culture conditions was impaired, the proportion of apoptosis increased, and myotube differentiation was impaired. In summary, ArfGAP3 regulates COPI-associated vesicle and GSVs transport and affects the proliferation and differentiation ability of myoblasts by influencing glucose uptake, thereby modulating the repair process after skeletal muscle injury.