Intracellular Pathway Followed by the Insulin Receptor Covalently Coupled to 125I-photoreactive Insulin During Internalization and Recycling

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 1986 Mar 1

PMID 3512585

Citations 12

Authors

J L Carpentier

H Gazzano

E Van Obberghen

M Fehlmann

P Freychet

L Orci

Affiliations

Soon will be listed here.

Abstract

After it interacts with a specific receptor on the cell surface, insulin is internalized in its target cell by an adsorptive endocytotic process and eventually degraded in lysosomes. It was also recently shown that the initial surface interaction between the hormone and its receptor is followed by an internalization of the receptor, which later is recycled back to the cell surface. In the present study the insulin receptor was tagged with a 125I-photoreactive insulin analogue that can be covalently coupled to the insulin receptor by ultraviolet irradiation. Using this tool we could trace by quantitative electron microscope autoradiography the intracellular pathway followed by this labeled receptor. The quantitative analysis of the intracellular distribution of the labeled material as a function of incubation time at 37 degrees C supports the following sequence of events: association first with clear vesicles, second with multivesicular bodies, third with dense bodies, and fourth, a return to the cell surface via clear vesicles. This insulin receptor recycling process is inhibited by monensin but unaffected by cycloheximide.

Citing Articles

Network medicine-travelling with the insulin receptor: Encounter of the second type.

Boutchueng-Djidjou M, Faure R EClinicalMedicine. 2019; 13:14-20.

PMID: 31517259 PMC: 6734015. DOI: 10.1016/j.eclinm.2019.07.007.

Reciprocal regulation of endocytosis and metabolism.

Antonescu C, McGraw T, Klip A Cold Spring Harb Perspect Biol. 2014; 6(7):a016964.

PMID: 24984778 PMC: 4067987. DOI: 10.1101/cshperspect.a016964.

Robert Feulgen Prize Lecture 1993. The journey of the insulin receptor into the cell: from cellular biology to pathophysiology.

Carpentier J Histochemistry. 1993; 100(3):169-84.

PMID: 8244769 DOI: 10.1007/BF00269090.

Insulin receptor internalization: molecular mechanisms and physiopathological implications.

Carpentier J Diabetologia. 1994; 37 Suppl 2:S117-24.

PMID: 7821727 DOI: 10.1007/BF00400835.

Ultrastructural evidence for the accumulation of insulin in nuclei of intact 3T3-L1 adipocytes by an insulin-receptor mediated process.

Smith R, JARETT L Proc Natl Acad Sci U S A. 1987; 84(2):459-63.

PMID: 3540967 PMC: 304227. DOI: 10.1073/pnas.84.2.459.

References

Schneider Y, Tulkens P, DE DUVE C, Trouet A . Fate of plasma membrane during endocytosis. II. Evidence for recycling (shuttle) of plasma membrane constituents. J Cell Biol. 1979; 82(2):466-74. PMC: 2110464. DOI: 10.1083/jcb.82.2.466. View

Carpentier J, Gorden P, Freychet P, Le Cam A, Orci L . Lysosomal association of internalized 125I-insulin in isolated rat hepatocytes. Direct demonstration by quantitative electron microscopic autoradiography. J Clin Invest. 1979; 63(6):1249-61. PMC: 372074. DOI: 10.1172/JCI109420. View

Kaplan J . Evidence for reutilization of surface receptors for alpha-macroglobulin.protease complexes in rabbit alveolar macrophages. Cell. 1980; 19(1):197-205. DOI: 10.1016/0092-8674(80)90401-8. View

Stahl P, Schlesinger P, Sigardson E, RODMAN J, Lee Y . Receptor-mediated pinocytosis of mannose glycoconjugates by macrophages: characterization and evidence for receptor recycling. Cell. 1980; 19(1):207-15. DOI: 10.1016/0092-8674(80)90402-x. View

Steer C, ASHWELL G . Studies on a mammalian hepatic binding protein specific for asialoglycoproteins. Evidence for receptor recycling in isolated rat hepatocytes. J Biol Chem. 1980; 255(7):3008-13. View

Van Leuven F, Cassiman J, Van Den Berghe H . Primary amines inhibit recycling of alpha 2M receptors in fibroblasts. Cell. 1980; 20(1):37-43. DOI: 10.1016/0092-8674(80)90232-9. View

Gonzalez-Noriega A, Grubb J, Talkad V, Sly W . Chloroquine inhibits lysosomal enzyme pinocytosis and enhances lysosomal enzyme secretion by impairing receptor recycling. J Cell Biol. 1980; 85(3):839-52. PMC: 2111452. DOI: 10.1083/jcb.85.3.839. View

Muller W, Steinman R, COHN Z . The membrane proteins of the vacuolar system. II. Bidirectional flow between secondary lysosomes and plasma membrane. J Cell Biol. 1980; 86(1):304-14. PMC: 2110648. DOI: 10.1083/jcb.86.1.304. View

Karin M, Mintz B . Receptor-mediated endocytosis of transferrin in developmentally totipotent mouse teratocarcinoma stem cells. J Biol Chem. 1981; 256(7):3245-52. View

10.

Schneider Y, DE DUVE C, Trouet A . Fate of plasma membrane during endocytosis. III. Evidence for incomplete breakdown of immunoglobulin in lysosomes of cultured fibroblasts. J Cell Biol. 1981; 88(2):380-7. PMC: 2111743. DOI: 10.1083/jcb.88.2.380. View

11.

Basu S, Goldstein J, Anderson R, Brown M . Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts. Cell. 1981; 24(2):493-502. DOI: 10.1016/0092-8674(81)90340-8. View

12.

Pastan I, Willingham M . Journey to the center of the cell: role of the receptosome. Science. 1981; 214(4520):504-9. DOI: 10.1126/science.6170111. View

13.

Zigmond S, Sullivan S, Lauffenburger D . Kinetic analysis of chemotactic peptide receptor modulation. J Cell Biol. 1982; 92(1):34-43. PMC: 2111993. DOI: 10.1083/jcb.92.1.34. View

14.

Schwartz A, Fridovich S, Lodish H . Kinetics of internalization and recycling of the asialoglycoprotein receptor in a hepatoma cell line. J Biol Chem. 1982; 257(8):4230-7. View

15.

Fehlmann M, Carpentier J, Le Cam A, Thamm P, Saunders D, BRANDENBURG D . Biochemical and morphological evidence that the insulin receptor is internalized with insulin in hepatocytes. J Cell Biol. 1982; 93(1):82-7. PMC: 2112115. DOI: 10.1083/jcb.93.1.82. View

16.

Tycko B, Maxfield F . Rapid acidification of endocytic vesicles containing alpha 2-macroglobulin. Cell. 1982; 28(3):643-51. DOI: 10.1016/0092-8674(82)90219-7. View

17.

Wilcox D, Kitson R, WIDNELL C . Inhibition of pinocytosis in rat embryo fibroblasts treated with monensin. J Cell Biol. 1982; 92(3):859-64. PMC: 2112029. DOI: 10.1083/jcb.92.3.859. View

18.

Fehlmann M, Le Marchand-Brustel Y, Van Obberghen E, BRANDENBURG D, Freychet P . Photoaffinity labelling of the insulin receptor in intact rat hepatocytes, mouse soleus muscle, and cultured human lymphocytes. Diabetologia. 1982; 23(5):440-4. DOI: 10.1007/BF00260959. View

19.

Geuze H, Slot J, Strous G, Lodish H, Schwartz A . Intracellular site of asialoglycoprotein receptor-ligand uncoupling: double-label immunoelectron microscopy during receptor-mediated endocytosis. Cell. 1983; 32(1):277-87. DOI: 10.1016/0092-8674(83)90518-4. View

20.

Gorden P, Carpentier J, MOULE M, Yip C, Orci L . Direct demonstration of insulin receptor internalization. A quantitative electron microscopic study of covalently bound 125I-photoreactive insulin incubated with isolated hepatocytes. Diabetes. 1982; 31(7):659-62. DOI: 10.2337/diab.31.7.659. View