Diacytosis of 125I-asialoorosomucoid by rat hepatocytesa. A non-lysosomal pathway insensitive to inhibition by inhibitors of ligand degradation

Chang, Ta‐Min; Kullberg, Deborah W.

doi:10.1016/0167-4889(84)90082-x

Cited by 26 publications

(4 citation statements)

References 28 publications

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“…Even at 50 p M , however, there was a significant measurable rate of continuous degradation of about 7% of the control rate, indicating that some internalized 1251-ASOR can still be dissociated and delivered to a degradative compartment (e.g., lysosomes). A residual rate of asialoglycoprotein catabolism in the presence of monensin has also been observed in several other studies (Grinde, 1983;Berg et al, 1983;Chang and Kullberg, 1984). This result, although not compelling, is consistent with the existence of two ligand-processing pathways for the Gal receptor system (Weigel, 1987;Weigel et al, 1986).…”

Section: Resultssupporting

confidence: 85%

Monensin inhibits ligand dissociation only transiently and partially and distinguishes two galactosyl receptor pathways in isolated rat hepatocytes

Oka¹,

Weigel²

1987

Journal Cellular Physiology

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Monensin has been shown to inhibit the dissociation of internalized asialoorosomucoid (ASOR) from galactosyl (Gal) receptors in hepatocytes (Harford et al., J. Cell. Biol., 96:1824, 1983). Examination of the long-term kinetics of dissociation of a single round of surface-bound 125I-ASOR in the presence of monensin revealed, however, that dissociation resumed after a lag of 30-40 min. Dissociation proceeded slowly with apparent first order kinetics (k = 0.006-0.022 min-1) and reached a plateau after 4 h, both in freshly isolated cells in suspension and in cells cultured for 24 h. Only a portion of the ligand bound to surface Gal receptors was capable of dissociating. The degree of dissociation was correlated with the expression of a subpopulation of receptors we have recently designated as state 1 Gal receptors (Weigel et al., Biochem. Biophys. Res. Commun. 140:43, 1986). The recovery and dissociation of a portion of 125I-ASOR-receptor complexes after the lag period is not due to a depletion of monensin, since a second addition of the drug has no affect once dissociation resumes. Furthermore, as assessed by the accumulation of the fluorescent dye acridine orange, cells have not recovered the ability to acidify intracellular compartments during the time that dissociation occurs. The results support a model for the hepatic Gal receptor system, in which there are two functionally different receptor populations, recycling pathways, and ligand processing pathways. Monensin blocks dissociation of 125I-ASOR from receptors in the major pathway completely. In the minor pathway dissociation proceeds to completion only after a lag. In this minor pathway monensin appears to temporarily delay a maturation or translocation process that must occur prior to dissociation. We conclude that the observed dissociation in the presence of monensin cannot be mediated by low pH, or by pH or pNa gradients.

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Section: Resultssupporting

confidence: 85%

Monensin inhibits ligand dissociation only transiently and partially and distinguishes two galactosyl receptor pathways in isolated rat hepatocytes

Oka¹,

Weigel²

1987

Journal Cellular Physiology

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“…1B, where FITC-and 125 I-ASOR were internalized at 377C to label late (peak fraction #46) and early (peak fraction #42) endosomes, respectively. The two peaks (fraction #42 -corresponding to early and fractions #46 -corresponding to late endosomes) seen for 125 I-ASOR are presumably due to recycling of 125 I-ASOR during the marker-free perfusion [46]. When the temperature is then shifted to 167C marker is or 6 x 10 7 cpm/70 mL KHB (B)) was followed by chase with marker-free medium for (A) 11 min or (B) 7 min at 377C, after which livers were rapidly cooled to 167C.…”

Section: The Lysosomal But Not the Transcytotic Route Involves A Secomentioning

confidence: 97%

Different temperature sensitivity of endosomes involved in transport to lysosomes and transcytosis in rat hepatocytes: Analysis by free-flow electrophoresis

Ellinger¹,

Klapper²,

Courtoy³

et al. 2002

Electrophoresis

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Endocytosis at reduced temperature has been used to define and characterize endosome subpopulations. Thus, the temperature sensitivity of endosome subpopulations involved in transport to lysosomes and transcytosis in rat hepatocytes was analyzed applying endosome labeling in the isolated perfused rat liver with route-specific ligands in combination with temperature shift protocols. Free-flow electrophoresis (FFE) that separates membranes and organelles based on their surface charge was then applied to isolate functional endosomes. Using asialoorosomucoid (ASOR) and polymeric immunoglobulin A (pIgA) as specific ligands of the lysosomal and transcytotic route, respectively, two distinct endosome subpopulations along either pathway were separated by FFE. Upon a short (1-3 min) internalization at 37 degrees C, 125I-ASOR and fluorescein isothiocyanate (FITC)-pIgA were colocalized in common early endosomes. Following a 5-10 min chase of the ligands at 37 degrees C endosomes labeled with 125I-ASOR were separated from endosomes labeled with FITC-pIgA, indicative of two distinct late compartments along the lysosomal and transcytotic route. Internalization at 16 degrees C resulted in accumulation of both ligands in common early endosomes and, consequently, in inhibition of transport to lysosomes and transcytosis. When 125I-ASOR or 125I-pIgA were first chased into late compartments at 37 degrees C and the temperature was subsequently lowered to 16 degrees C, biliary secretion of 125I-ASOR-derived counts was arrested, while biliary output of 125I-pIgA continued. In summary, ASOR en route to lysosomes can be blocked in early as well as in late endosomes at 16 degrees C, while biliary secretion of pIgA cannot be prevented by temperature reduction once the ligand had been transferred from early to late compartments.

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“…Those previous studies provided the notion that after internalization, ligand-receptor complexes can recycle through chloroquine-insensitive pathway and finally be degraded via chloroquine-sensitive lysosomal compartments [ 24 , 25 ]. Accumulating evidence suggests that several types of ligand-receptor complexes, including for EGF, insulin, and asialoglycoprotein, also recycle through the chloroquine-insensitive pathway [ 31 , 114 , 119 , 120 , 122 , 123 ].…”

Section: Structural Topology and Internalization Of Npramentioning

confidence: 99%

Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs

Pandey

2015

Membranes

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The targeted endocytosis and redistribution of transmembrane receptors among membrane-bound subcellular organelles are vital for their correct signaling and physiological functions. Membrane receptors committed for internalization and trafficking pathways are sorted into coated vesicles. Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and elicit the generation of intracellular second messenger cyclic guanosine 3',5'-monophosphate (cGMP), which lowers blood pressure and incidence of heart failure. After ligand binding, the receptor is rapidly internalized, sequestrated, and redistributed into intracellular locations. Thus, NPRA is considered a dynamic cellular macromolecule that traverses different subcellular locations through its lifetime. The utilization of pharmacologic and molecular perturbants has helped in delineating the pathways of endocytosis, trafficking, down-regulation, and degradation of membrane receptors in intact cells. This review describes the investigation of the mechanisms of internalization, trafficking, and redistribution of NPRA compared with other cell surface receptors from the plasma membrane into the cell interior. The roles of different short-signal peptide sequence motifs in the internalization and trafficking of other membrane receptors have been briefly reviewed and their potential significance in the internalization and trafficking of NPRA is discussed.

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Diacytosis of 125I-asialoorosomucoid by rat hepatocytesa. A non-lysosomal pathway insensitive to inhibition by inhibitors of ligand degradation

Cited by 26 publications

References 28 publications

Monensin inhibits ligand dissociation only transiently and partially and distinguishes two galactosyl receptor pathways in isolated rat hepatocytes

Monensin inhibits ligand dissociation only transiently and partially and distinguishes two galactosyl receptor pathways in isolated rat hepatocytes

Different temperature sensitivity of endosomes involved in transport to lysosomes and transcytosis in rat hepatocytes: Analysis by free-flow electrophoresis

Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs

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