Receptor — Mediated Endocytosis and Receptor/Ligand Sorting

A number of peptide hormones have been shown to undergo receptor-mediated endocytosis (RME). RME involves the internalization of receptor-ligand complexes followed by delivery to an intracellular compartment, the endosome, from which ligands or receptors can be delivered to lysosomes or other cellular destinations. Vasopressin, a peptide hormone that plays a role in kidney and vascular physiology, has recently been demonstrated to undergo RME in LLC-PK1 and A10 cells, which express V2- and V1-type vasopressin receptors, respectively. Fluorescent vasopressin analogues are internalized by RME from the basolateral surface of polarized LLC-PK1 cells. The precise role of RME in vasopressin action is uncertain, but it is likely that it is involved in the desensitization of target cells by altering the number of cell surface vasopressin receptors. Alterations in the rate of RME may alter the response of the cell to vasopressin. Fluorescent and biotinylated vasopressins are useful tools for the study of this process.

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Intracellular site of asialoglycoprotein receptor-ligand uncoupling: Double-label immunoelectron microscopy during receptor-mediated endocytosis

Cell ◽

10.1016/0092-8674(83)90518-4 ◽

1983 ◽

Vol 32 (1) ◽

pp. 277-287 ◽

Cited By ~ 467

Author(s):

Hans J. Geuze ◽

Jan Willem Slot ◽

Ger J.A.M. Strous ◽

Harvey F. Lodish ◽

Alan L. Schwartz

Keyword(s):

Immunoelectron Microscopy ◽

Asialoglycoprotein Receptor ◽

Receptor Ligand ◽

Receptor Mediated Endocytosis ◽

Double Label

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Mannose-specific endocytosis receptor of alveolar macrophages: demonstration of two functionally distinct intracellular pools of receptor and their roles in receptor recycling.

The Journal of Cell Biology ◽

10.1083/jcb.92.2.417 ◽

1982 ◽

Vol 92 (2) ◽

pp. 417-424 ◽

Cited By ~ 120

Author(s):

C Tietze ◽

P Schlesinger ◽

P Stahl

Keyword(s):

Cell Surface ◽

Ammonium Chloride ◽

Alveolar Macrophages ◽

Binding Activity ◽

Dissociation Rate ◽

Receptor Recycling ◽

Surface Binding ◽

Receptor Ligand ◽

Receptor Mediated Endocytosis ◽

Weak Bases

Receptor-mediated endocytosis of rat preputial beta-glucuronidase and the glycoconjugate mannose-BSA by rat alveolar macrophages is inhibited by chloroquine and ammonium chloride. We have previously reported that these drugs cause a loss of cell surface binding activity and that they do not inhibit internalization of receptor ligand complexes when incubated with cells at 37 degrees C. In this report we more clearly delineate the intracellular site of weak base inhibition of receptor recycling and the mechanism of that inhibition. From our analysis of the kinetics of ligand transport we conclude that there are two functionally distinct intracellular pools of receptor. One of these, the cycling pool, is not sensitive to the presence of weak bases, and receptor-ligand complexes return from this pool to the cell surface intact. The second pool is responsible for the time-dependent intracellular delivery of ligand to acid vesicles, which is inhibited by weak bases. Chloroquine and ammonium chloride appear to inhibit the dissociation of receptor-ligand complexed in this second pool and thereby the production of free receptors for the continuation of receptor-mediated endocytosis. We examine the internalization and binding of ligand in normal and paraformaldehyde-treated cells and find that these are strongly affected by pH. In particular, the dissociation rate of receptor ligand complexes is enhanced greater than 7.5 fold by lowering the medium pH from 7 to 6. From these results we propose that weak bases raise the pH of acid intracellular compartments, slowing the rate of receptor-ligand dissociation and thereby reducing the cellular pool of free receptors available for further uptake of ligand. In addition, we demonstrate that receptor-ligand complexes cannot return to the cell surface from the amine-sensitive (acid) intracellular pool that led us to call this the nonreleasable pool. This final observation indicates that receptor movements through these two pools are functionally distinct processes.

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Ultrastructural study of cytoskeletal interactions with endosomes in macrophages by quickfreezing and deep-etching method

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100160431 ◽

1990 ◽

Vol 48 (3) ◽

pp. 576-577

Author(s):

Takeshi Baba ◽

Nobuki Shiozawa ◽

Masao Hotch ◽

Shinichi Ohno

Keyword(s):

Immune Complex ◽

Ultrastructural Study ◽

Fc Receptor ◽

Coated Pits ◽

Deep Etching ◽

Receptor Mediated Endocytosis ◽

Etching Method ◽

Quick Freezing

Endosomes are vesicular or tubular organelles that play important roles in transports of receptors and receptor―bound ligands during receptor-mediated endocytosis. The mechanisms of endocytic transports from clathrin-coated pits to lysosomes have been studied by many investigators. However, few studies were reported about the interactions between endosomes and cytoskeletons. In this study, Fc-receptor-mediated endocytosis in macrophages are investigated by quick-freezing and deep-etching (QF-DE) method combined with gold-labeled immune complex and “replica scraping method”.

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Vergleich von Blutfluß und Benzodiazepin-Rezeptorverteilung bei fokaler Epilepsie: Vorläufige Ergebnisse einer SPECT-Studie

Nuklearmedizin ◽

10.1055/s-0038-1629489 ◽

1989 ◽

Vol 28 (05) ◽

pp. 181-186

Author(s):

A. Ludolph ◽

O. Schober ◽

G. Lottes ◽

I. Böttger ◽

H.-F. Beer ◽

...

Keyword(s):

Human Brain ◽

Receptor Binding ◽

Brain Area ◽

Brain Perfusion ◽

Partial Epilepsy ◽

Cerebral Lesion ◽

Receptor Ligand ◽

Receptor Mapping ◽

Hmpao Spect ◽

99Mtc Hmpao

99mTc-HMPAO-SPECT and SPECT with the 123I-labelled benzodiazepine (Bz) receptor ligand Ro 16-0154 were performed in 10 patients suffering from partial epilepsy, without cerebral lesion in MRT or CT. 2 h p.i. of Ro 16-0154 the distribution of activity correlated with the known distribution of Bz- receptors in the human brain. Perfusion and receptor-binding were found decreased in 7 patients of each study in the suspicious brain-area. 123l-labelled Ro 16-0154 is suitable for Bz-receptor mapping by SPECT. The decrease of Bz-receptor binding in epileptic foci, as described in PET-studies, was also detected by SPECT in 7 of 10 patients.

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Modulation of Platelet Activation by Native DNA – Initial Description of Platelet Receptor Type, Number and Discrimination for Native DNA

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650184 ◽

1981 ◽

Vol 45 (03) ◽

pp. 263-266 ◽

Cited By ~ 5

Author(s):

B A Fiedel ◽

M E Frenzke

Keyword(s):

Platelet Aggregation ◽

Human Platelets ◽

Scatchard Analysis ◽

Type Number ◽

Single Class ◽

Receptor Ligand ◽

Platelet Receptor ◽

Platelet Binding ◽

Ligand Interactions ◽

Initial Description

SummaryNative DNA (dsDNA) induces the aggregation of isolated human platelets. Using isotopically labeled dsDNA (125I-dsDNA) and Scatchard analysis, a single class of platelet receptor was detected with a KD = 190 pM and numbering ~275/platelet. This receptor was discriminatory in that heat denatured dsDNA, poly A, poly C, poly C · I and poly C · poly I failed to substantially inhibit either the platelet binding of, or platelet aggregation induced by, dsDNA; by themselves, these polynucleotides were ineffective as platelet agonists. However, poly G, poly I and poly G · I effectively and competitively inhibited platelet binding of the radioligand, independently activated the platelet and when used at a sub-activating concentration decreased the extent of dsDNA stimulated platelet aggregation. These data depict a receptor on human platelets for dsDNA and perhaps certain additional polynucleotides and relate receptor-ligand interactions to a physiologic platelet function.

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