Simultaneous redistribution of mannose 6-phosphate and transferrin receptors by insulin-like growth factors and phorbol ester

Abstract

Insulin-like growth factors I and II (IGF-I and IGF-II) and phorbol ester are known to induce in fibroblasts a rapid redistribution of mannose 6-phosphate (M6P)/IGF II-receptors to the cell surface. We compared the redistribution of the M6P/IGF-II receptor with that of the 46 kDa M6P receptor (MPR46) and of receptors for transferrin, low-density lipoprotein (LDL) and epidermal growth factor (EGF) in human fibroblasts under the influence of these effectors. None of the effectors altered the surface expression of receptors for LDL or EGF, which are predominantly located at the cell surface. IGF-I, IGF-II and phorbol ester increased the surface expression of the M6P/IGF-II receptor and of MPR46. The concentration of the transferrin receptor at the cell surface was increased only by IGF-I and IGF-II, with similar kinetics as for the M6P/IGF-II receptor, suggesting that the same mechanism causes redistribution. The increased surface expression of M6P receptors was accompanied by an increased uptake of receptor ligands. The number of transferrin receptors did not correlate with iron uptake, although neither the rate nor the extent of transferrin internalization was changed. These results indicate that the redistribution of several endocytic receptors induced by IGF-I, IGF-II and phorbol ester shows selectivity, and that the uptake of receptor ligand may become uncoupled from the surface expression of the receptors via distinct mechanisms.