Low-density-lipoprotein receptors in human fibroblasts are not degraded in lysosomes

Livia A Casciola Rosen, K. I. Grant, W. Gevers, G. A. Coetzee, D. R. Van Der Westhuyzen

Research output: Contribution to journalArticle

Abstract

The rate of degradation of low-density-lipoprotein (LDL) receptors was measured in cultured human skin fibroblasts by [35S]methionine pulse-chase experiments. The half-life of LDL receptors was unaltered by inclusion of LDL in the medium (t( 1/2 ) 11 h). Neither lysosomotropic inhibitors (chloroquine or NH4Cl) nor leupeptin inhibited the rate of receptor degradation in the absence of ligand. In cells incubated at 18°C to inhibit the delivery of internalized ligands from endocytic vesicles to lysosomes, receptor degradation continued but at the expected rate of about six times lower than that at 37°C. Mutant LDL receptors defective in internalization were degraded at the same rate as normal receptors, suggesting that receptor internalization and recycling are not required for basal turnover. We conclude that the rate-limiting steps for, and probably the whole pathway of, degradation of normal LDL receptors does not take place in lysosomes.

Original languageEnglish (US)
Pages (from-to)681-683
Number of pages3
JournalBiochemical Journal
Volume262
Issue number2
StatePublished - 1989
Externally publishedYes

Fingerprint

LDL Receptors
Fibroblasts
Lysosomes
Degradation
Ligands
Transport Vesicles
Chloroquine
Recycling
LDL Lipoproteins
Methionine
Half-Life
Skin
human LDLR protein
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Casciola Rosen, L. A., Grant, K. I., Gevers, W., Coetzee, G. A., & Van Der Westhuyzen, D. R. (1989). Low-density-lipoprotein receptors in human fibroblasts are not degraded in lysosomes. Biochemical Journal, 262(2), 681-683.

Low-density-lipoprotein receptors in human fibroblasts are not degraded in lysosomes. / Casciola Rosen, Livia A; Grant, K. I.; Gevers, W.; Coetzee, G. A.; Van Der Westhuyzen, D. R.

In: Biochemical Journal, Vol. 262, No. 2, 1989, p. 681-683.

Research output: Contribution to journalArticle

Casciola Rosen, LA, Grant, KI, Gevers, W, Coetzee, GA & Van Der Westhuyzen, DR 1989, 'Low-density-lipoprotein receptors in human fibroblasts are not degraded in lysosomes', Biochemical Journal, vol. 262, no. 2, pp. 681-683.
Casciola Rosen LA, Grant KI, Gevers W, Coetzee GA, Van Der Westhuyzen DR. Low-density-lipoprotein receptors in human fibroblasts are not degraded in lysosomes. Biochemical Journal. 1989;262(2):681-683.
Casciola Rosen, Livia A ; Grant, K. I. ; Gevers, W. ; Coetzee, G. A. ; Van Der Westhuyzen, D. R. / Low-density-lipoprotein receptors in human fibroblasts are not degraded in lysosomes. In: Biochemical Journal. 1989 ; Vol. 262, No. 2. pp. 681-683.
@article{f5b79446d4b24017a997a538c6ebdcc3,
title = "Low-density-lipoprotein receptors in human fibroblasts are not degraded in lysosomes",
abstract = "The rate of degradation of low-density-lipoprotein (LDL) receptors was measured in cultured human skin fibroblasts by [35S]methionine pulse-chase experiments. The half-life of LDL receptors was unaltered by inclusion of LDL in the medium (t( 1/2 ) 11 h). Neither lysosomotropic inhibitors (chloroquine or NH4Cl) nor leupeptin inhibited the rate of receptor degradation in the absence of ligand. In cells incubated at 18°C to inhibit the delivery of internalized ligands from endocytic vesicles to lysosomes, receptor degradation continued but at the expected rate of about six times lower than that at 37°C. Mutant LDL receptors defective in internalization were degraded at the same rate as normal receptors, suggesting that receptor internalization and recycling are not required for basal turnover. We conclude that the rate-limiting steps for, and probably the whole pathway of, degradation of normal LDL receptors does not take place in lysosomes.",
author = "{Casciola Rosen}, {Livia A} and Grant, {K. I.} and W. Gevers and Coetzee, {G. A.} and {Van Der Westhuyzen}, {D. R.}",
year = "1989",
language = "English (US)",
volume = "262",
pages = "681--683",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "2",

}

TY - JOUR

T1 - Low-density-lipoprotein receptors in human fibroblasts are not degraded in lysosomes

AU - Casciola Rosen, Livia A

AU - Grant, K. I.

AU - Gevers, W.

AU - Coetzee, G. A.

AU - Van Der Westhuyzen, D. R.

PY - 1989

Y1 - 1989

N2 - The rate of degradation of low-density-lipoprotein (LDL) receptors was measured in cultured human skin fibroblasts by [35S]methionine pulse-chase experiments. The half-life of LDL receptors was unaltered by inclusion of LDL in the medium (t( 1/2 ) 11 h). Neither lysosomotropic inhibitors (chloroquine or NH4Cl) nor leupeptin inhibited the rate of receptor degradation in the absence of ligand. In cells incubated at 18°C to inhibit the delivery of internalized ligands from endocytic vesicles to lysosomes, receptor degradation continued but at the expected rate of about six times lower than that at 37°C. Mutant LDL receptors defective in internalization were degraded at the same rate as normal receptors, suggesting that receptor internalization and recycling are not required for basal turnover. We conclude that the rate-limiting steps for, and probably the whole pathway of, degradation of normal LDL receptors does not take place in lysosomes.

AB - The rate of degradation of low-density-lipoprotein (LDL) receptors was measured in cultured human skin fibroblasts by [35S]methionine pulse-chase experiments. The half-life of LDL receptors was unaltered by inclusion of LDL in the medium (t( 1/2 ) 11 h). Neither lysosomotropic inhibitors (chloroquine or NH4Cl) nor leupeptin inhibited the rate of receptor degradation in the absence of ligand. In cells incubated at 18°C to inhibit the delivery of internalized ligands from endocytic vesicles to lysosomes, receptor degradation continued but at the expected rate of about six times lower than that at 37°C. Mutant LDL receptors defective in internalization were degraded at the same rate as normal receptors, suggesting that receptor internalization and recycling are not required for basal turnover. We conclude that the rate-limiting steps for, and probably the whole pathway of, degradation of normal LDL receptors does not take place in lysosomes.

UR - http://www.scopus.com/inward/record.url?scp=0024469541&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024469541&partnerID=8YFLogxK

M3 - Article

C2 - 2803276

AN - SCOPUS:0024469541

VL - 262

SP - 681

EP - 683

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 2

ER -