Protein Degradation in the Plasma Membrane of Regenerating Liver and Morris Hepatomas

Tauber, Rudolf; Reutter, Werner

doi:10.1111/j.1432-1033.1978.tb12065.x

Cited by 66 publications

(32 citation statements)

References 48 publications

(13 reference statements)

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“…(10.4 Ci/mmol; 0.5 mCi/100 g body mass) (0); 2 h later, and then every 12 h, 50 mg/100 g body mass of unlabelled precursor was given as a chase. Then 12,24,36,48, and 72 h after labelling, plasma membranes were prepared from the pooled hepatomas of three rats. The glycoproteins were immunoprecipitated from the isolated plasma membranes as described in Materials and Methods.…”

Section: Discussionmentioning

confidence: 99%

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Rapid intramolecular turnover of N‐linked glycans in plasma membrane glycoproteins

Tauber

Park

Becker

et al. 1989

European Journal of Biochemistry

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Plasma membrane glycoproteins of rat hepatocytes undergo a rapid terminal deglycosylation in that the terminal sugars of the oligosaccharide side chains are rapidly removed from the otherwise intact glycoproteins [Tauber, R., Park, C. S. Proc. Natl Acad. Sci. USA 80,. The present paper demonstrates that this rapid intramolecular turnover of plasma membrane glycoproteins is not restricted to peripheral sugars but, in contrast to liver, in hepatoma the core sugars of the oligosaccharide chains are also involved. lntramolecular turnover was measured in Morris hepatoma 7777 in five plasma membrane glycoproteins with M , of 85000 (hgp85), 105000 (hgpl05), 115000 (hgp115), 125000 (hgp125), 175000 (hgp175) (hgp = hepatoma glycoprotein) that were isolated and purified to homogeneity by concanavalin-A -Sepharose affinity chromatography and semipreparative SDS gel electrophoresis. Analysis of the carbohydrates of hgp85, hgpl05, hgpll5 and hgp125 revealed the presence of N-linked oligosaccharides containing L-fucose, D-galactose, Dmannose and N-acetyl-D-glucosamine, but only of trace amounts of N-acetyl-u-galactosamine; hgpl75 additionally contained significant amounts of N-acetyl-D-galactosamine, indicating the presence of both N-and 0-linked oligosaccharides. As shown by digestion with endoglucosaminidase H, the N-linked oligosaccharides of hgpl05, hgpll5, hgp125 and hgp175 were of the complex type, whereas hgp85 also contained oligosacharides of the highmannose type. Half-lives of the turnover of the oligosacharide chains and of the protein backbone of the five glycoproteins were measured in the plasma membrane in pulse-chase experiments in vivo, using ~-[~H]fucose as a marker of terminal sugars, ~-[~H]mannose as marker of a core sugar and ~-[~H]leucine for labelling the protein backbone. Protein backbones of the five glycoproteins were degraded with individual half-lives ranging over 41 -90 h with a mean of 66 h. Compared to the degradation of the polypeptide backbone, both the terminal sugar L-fucose and the core sugar D-mannose turned over with much shorter half-lives averaging about 20 h in the five glycoproteins. The data show that, conversely to liver, within plasma membrane glycoproteins of hepatoma not only peripheral sugars but also core sugars of the oligosaccharides are split off during the life-span of the protein backbone. It may therefore be assumed that this reprocessing of plasma membrane glycoproteins is sensitive to malignant transformation.Individual glycoproteins of the hepatocyte plasma membrane undergo continuous turnover, being degraded upon internalization and replaced by newly synthesized glycoproteins [1 -31. Superimposed upon this basic turnover is an additional rapid intramolecular turnover of the terminal sugar residues of the oligosaccharides side chains. As recently shown for several glycoproteins, including dipeptidylpeptidase IV, the terminal sugars L-fucose and N-acetylneuraminic acid are lost from the glycoproteins three to four times faster compared with the degradation of the protei...

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Section: Discussionmentioning

confidence: 99%

“…Membrane purity was checked by electron microscopy and by the assay of marker enzymes as already described [12]. Protein was determined by the method of Lowry et al [14] with bovine serum albumin as a standard.…”

Section: Preparation Of Plasma Membranesmentioning

confidence: 99%

Rapid intramolecular turnover of N‐linked glycans in plasma membrane glycoproteins

Tauber

Park

Becker

et al. 1989

European Journal of Biochemistry

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“…Precursor fucose, as shown by several investigations [1][2][3][4], is efficiently incorporated by the rat liver into newly synthesized membrane glycoproteins. An intriguing feature of fucose (and sialic acid) in hepatic membrane glycoproteins is its short half-life as compared with that of the peptide moiety.…”

Section: Introductionmentioning

confidence: 99%

“…An intriguing feature of fucose (and sialic acid) in hepatic membrane glycoproteins is its short half-life as compared with that of the peptide moiety. This observation was first made for dipeptidylpeptidase IV [5], and then extended over five additional individual glycoproteins [6] by Reutter and co-workers [7,8]. Hepatoma cell-membrane glycoproteins, whether in situ or transferred to fibroblasts, exhibit an analogous behaviour [9].…”

Section: Introductionmentioning

confidence: 99%

Metabolic stability of the fucose in rat transferrin

Regoeczi

Chindemi

1987

FEBS Letters

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The metabolic behaviour of the chitobiose core fucose that is a natural constituent of a large proportion of rat transferrin molecules was studied in rats comparatively to that of the polypeptide portion of the glycoprotein by using appropriate labels ([aH]fucose and 125I) and affinity chromatographic techniques (lentilSepharose). No evidence was obtained to suggest that this residue is cleaved from the glycan in significant amounts before removal of the entire glycoprotein for catabolism. Similarly, p4C]fucose linked to GlcNAc residues in the antennae of human asialotransferrin was being eliminated in pigeons at the same rate as the polypeptide itself. It is concluded that in spite of transferrin's exposure to the cellular milieu, the fate of its fucose is distinctly different from that of the same in plasma membrane glycoproteins.Fucose; Glycoprotein metabolism; Transferrin

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“…This controlled liver cell proliferation causes a drastic inhibition of the degradation of cellular proteins [17] including plasma membrane proteins and glycoproteins [9,18,19]. Turnover studies of the different components of an isolated liver plasma membrane glycoprotein have not yet been performed in regenerating liver.…”

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confidence: 99%

Modification of the intramolecular turnover of terminal carbohydrates of dipeptidylaminopeptidase IV isolated from rat‐liver plasma membrane during liver regeneration

Kreisel

Reutter

Gerok

1984

European Journal of Biochemistry

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An intramolecular turnover of the terminal carbohydrates L-fucose, N-acetylneuraminic acid and D-galaCtOSe is a characteristic property of several liver plasma membrane glycoproteins, first demonstrated for dipeptidylaminopeptidase IV (EC 3.4.14.5., DPP IV). The core carbohydrates D-mannOSe and N-acetyl-D-glucosamine turn over like the polypeptide chain. The ratio of apparent half-lives of L-fucose and L-methionine of DPP IV is shifted from 0.17 in normal liver to 0.60 in regenerating liver. The ratio of half-lives of N-acetylneuraminic acid and L-methionine is only slightly changed from 0.43 in normal liver to 0.61 in regenerating liver. The ratio of apparent half-lives of D-mannose and L-methionine amounts to 0.80 in normal liver and 0.71 after partial hepatectomy. From this a drastic reduction of the intramolecular turnover of L-fucose on plasma membrane DPP IV in regenerating liver can be derived. The intramolecular N-acetylneuraminic acid turnover is affected to only a minor extent. D-Mannose turns over like the polypeptide in both normal and regenerating liver. The intramolecular L-fucose turnover may be involved in membrane glycoprotein recycling, which presumably is altered in regenerating liver. Additionally, L-fucose could regulate the rate of degradation of DPP IV, since core-fucosylated glycoproteins appear to be resistant to mammalian endo-N-acetylglucosaminidase.The glycoproteins of the hepatocyte plasma membrane are involved in a variety of functions such as enzymatic activity, antigenicity, receptor and transport function and cellular communication [l 1. Their actual concentration in the membrane depends on de novo synthesis, insertion into and removal from the membrane, including an eventual recycling, and degradation. Each of these processes is influenced by numerous endogenous and exogenous factors [2]. In contrast to other cell systems [3], the glycoproteins of liver and hepatoma plasma membrane are not turned over in bulk, but exhibit a marked intermolecular heterogeneity with respect to their individual turnover rates and half-lives [4 -1 I]. In previous publications we described an intramolecular heterogeneity in the turnover of dipeptidylaminopeptidase IV (DPP 1V) isolated from rat liver plasma membrane. The terminal carbohydrates L-fucose, N-acetylneuraminic acid and D-galactose possess half-lives much shorter than the polypeptide moiety. That is, terminal carbohydrates turn over several times during the life span of this glycoprotein [12,13]. The core carbohydrates D-mannose and N-acetyl-D-glucosamine behave similarly to the polypeptide [14]. Recently this effect was demonstrated for other plasma membrane glycoproteins of rat liver [15] and a hepatoma cell line [16].Rapid growth after partial hepatectomy is a condition with characteristic alterations of glycoprotein metabolism. This controlled liver cell proliferation causes a drastic inhibition of the degradation of cellular proteins [17] including plasma membrane proteins and glycoproteins [9,18,19]. Turnover studies of the different ...

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Protein Degradation in the Plasma Membrane of Regenerating Liver and Morris Hepatomas

Cited by 66 publications

References 48 publications

Rapid intramolecular turnover of N‐linked glycans in plasma membrane glycoproteins

Rapid intramolecular turnover of N‐linked glycans in plasma membrane glycoproteins

Metabolic stability of the fucose in rat transferrin

Modification of the intramolecular turnover of terminal carbohydrates of dipeptidylaminopeptidase IV isolated from rat‐liver plasma membrane during liver regeneration

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