Insulin-like growth factors I and II stimulate endocytosis but do not affect sorting of lysosomal enzymes in human fibroblasts.
The mannose 6-phosphate (Man-6-P)/insulin-like growth factor (IGF) II receptor has separate binding sites for Man-6-P and IGF II. It targets newly synthesized lysosomal enzymes from the Golgi to acidic pre-lysosomal organelles and mediates endocytosis of Man-6-P-containing ligands and IGF II. The two classes of ligands, Man-6-P and IGF II, as well as IGF I and the epidermal growth factor, induce in fibroblasts a transient redistribution of the receptor from internal membranes to the cell surface (Braulke, T., Tippmer, S., Neher, E., and von Figura, K. (1989) EMBO J. 8, 681-686). Here we show that the redistribution induced by IGF I and IGF II is accomplished without affecting the internalization rate of cell surface receptors. The redistribution results in an increased binding of ligands to the Man-6-P- and IGF II-binding sites of the receptor. Furthermore, the uptake of the lysosomal enzyme arylsulfatase A and of a Man-6-P neoglycoprotein is stimulated 2-3-fold by IGF I and IGF II, and this effect persists for at least 6 h. The IGF I- and IGF II-induced receptor redistribution does not affect the targeting of newly synthesized lysosomal enzymes. These results show that important functions of the Man-6-P/IGF II receptor such as binding and internalization of ligands can be up-regulated by the ligands of this receptor and other growth factors such as IGF I through redistribution of the receptor.
Braulke
T
T
University of Göttingen, Biochemie II, Federal Republic of Germany.
Tippmer
S
S
Chao
H J
HJ
von Figura
K
K
D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008360:Mannosephosphates / Q000378:metabolism / Q000494:pharmacology; D012867:Skin / Q000378:metabolism; D013002:Somatomedins / Q000494:pharmacology*; D013696:Temperature
D008360:Mannosephosphates; D013002:Somatomedins; C027693:mannose-6-phosphate; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D002553:Cerebroside-Sulfatase