INVOLVEMENT OF THE GLUT TRANSPORTER IN MYOGENIC REGULATION

We have recently demonstrated a close relationship between the GLUT3 t ransporter and the myogenic ability of rat skeletal L6 myoblasts [1]. This investigation examined the effects of over- and under-expression of the GLUT3 transporter on both biochemical and morphological differe ntiation. L6 transfectants expressing two to five times the normal L6 GLUT3 transcript level were impaired in the expression of myogenesis-a ssociated genes, such as myogenin, MLC, MHC and TnT, and in myotube fo rmation. Similar defects were also observed in myoblast mutants expres sing less than 20% of the normal GLUT3 level. Forced expression of an exogenous GLUT3 cDNA could partially rescue the myogenic defect of the se GLUT3(-) mutants. However, such myogenic defects were not observed in L6 GLUT3 antisense transfectants expressing 39% of the normal L6 GL UT3 level. These data suggest that myogenic differentiation will proce ed only within a critical level of the GLUT3 transporter. The optimal GLUT3 content for myogenesis ranges from around 2 x 10(5) to 5 x 10(5) molecules per cell in day 2 cultures; GLUT3 levels outside this range have a negative effect on myogenesis. Our data suggest that GLUT3 may regulate myogenesis by modulating the levels of signal transducers re quired for expression of myogenin and muscle-specific contractile prot ein genes.