Insulin-induced surface redistribution regulates internalization of the insulin receptor and requires its autophosphorylation.
The role of insulin-induced receptor autophosphorylation in its internalization was analyzed by comparing 125I-labeled insulin (125I-insulin) internalization in Chinese hamster ovary (CHO) cell lines transfected with normal (CHO.T) or mutated insulin receptors. In four cell lines with a defect of insulin-induced autophosphorylation, 125I-insulin internalization was impaired. By contrast, in CHO.T cells and in two other CHO cell lines with amino acid deletions or insertions that do not perturb autophosphorylation, 125I-insulin internalization was not affected. A morphological analysis showed that the inhibition is linked to the ligand-specific surface redistribution in which the insulin-receptor complexes leave microvilli and concentrate on nonvillous segments of the membrane where endocytosis occurs.
Carpentier
J L
JL
Department of Morphology, University of Geneva Medical Center, Switzerland.
Paccaud
J P
JP
Gorden
P
P
Rutter
W J
WJ
Orci
L
L
D000818:Animals; D001345:Autoradiography; D016466:CHO Cells; D006224:Cricetinae; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D004705:Endocytosis; D007328:Insulin / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D007328:Insulin; D010750:Phosphoproteins; D011972:Receptor, Insulin