The Phosphomannosyl Recognition System for Intracellular and Intercellular Transport of Lysosomal Enzymes

Sly, William S.; Hd, Fischer

doi:10.1002/jcb.1982.240180107

Cited by 364 publications

(154 citation statements)

References 76 publications

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“…Lysosomal enzymes, for example, are secreted from and re-enter cells by mannose-6-phosphate-mediated pathways. 8 With few exceptions 9,10 secretory proteins are translocated across the endoplasmic reticulum (ER) membrane during their synthesis. Such translocation is mediated by a hydrophobic signal sequence, a signal recognition protein (SRP), and an SRP receptor (docking protein) located in the ER.…”

Section: Discussionmentioning

confidence: 99%

Intercellular trafficking of VP22-GFP fusion proteins is not observed in cultured mammalian cells

Fang

Koch

et al. 1998

Gene Ther

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Herpes simplex virus type 1 (HSV-1) VP22 was recently fused proteins were localized to the nuclei of transfected reported to mediate intercellular trafficking of a protein cells. Quantitative analysis of GFP-positive cells, however, fused to the C-terminus of VP22. To explore the application showed no significant increase in intercellular protein trafof such trafficking, we constructed plasmids expressing ficking for cells transfected with either fusion protein comgreen fluorescent protein (GFP) fused to the C-terminus of pared with a lacZ-expressing plasmid. Our results suggest either wild-type VP22 or a 160 amino acid peptide from that the use of HSV-1 VP22 for mediating intercellular VP22. In vitro studies showed that the majority of both trafficking of transgene products is limited.

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Section: Discussionmentioning

confidence: 99%

Intercellular trafficking of VP22-GFP fusion proteins is not observed in cultured mammalian cells

Fang

Koch

et al. 1998

Gene Ther

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“…Although this binding could reflect an apolipoprotein B secretory system analogous to the mannose 6-phosphate receptor pathway for lysosomal enzymes [41], the importance and physiologic role of this alternative recognition remains to be elucidated. After 7 days in tissue culture, hepatocytes adhered to the tissue culture plates, flattened out and increased in size as shown by phase-contrast microscopy (left panel).…”

Section: Discussionmentioning

confidence: 99%

Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects

Hoeg

Edge

Demosky

et al. 1986

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metaboli

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The profoundly elevated concentrations of low-density lipoproteins (LDL) present in homozygous familial hypercholesterolemia lead to symptomatic cardiovascular disease and death by early adulthood. Studies conducted in nonhepatic tissues demonstrated defective cellular recognition and metabolism of LDL in these patients. Since mammalian liver removes at least half of the LDL in the circulation, the metabolism of LDL by cultured hepatocytes isolated from familial hypercholesterolemic homozygotes was compared to hepatocytes from normal individuals. Fibroblast studies demonstrated that the familial hypercholesterolemic subjects studied were LDL receptor-negative (less than 1% normal receptor activity) and LDL receptor-defective (18% normal receptor activity). Cholesterol-depleted hepatocytes from normal subjects bound and internalized 125 I-labeled LDL (B max = 2.2 μg LDL/mg cell protein). Preincubation of normal hepatocytes with 200 μg/ml LDL reduced binding and internalization by approx. 40%. In contrast, 125 I-labeled LDL binding and internalization by receptor-negative familial hypercholesterolemic hepatocytes was unaffected by cholesterol loading and considerably lower than normal. This residual LDL uptake could not be ascribed to fluid phase endocytosis as determined by [ 14 C]sucrose uptake. The residual LDL binding by familial hypercholesterolemia hepatocytes led to a small increase in hepatocyte cholesterol content which was relatively ineffective in reducing hepatocyte 3-hydroxy-3-methylglutaryl-CoA reductase activity. Receptordefective familial hypercholesterolemia hepatocytes retained some degree of regulatable 125 Ilabeled LDL uptake, but LDL uptake did not lead to normal hepatocyte cholesterol content or 3-hydroxy-3-methylglutaryl-CoA reductase activity. These combined results indicate that the LDL receptor abnormality present in familial hypercholesterolemia fibroblasts reflects deranged hepatocyte LDL recognition and metabolism. In addition, a low-affinity, nonsaturable uptake process for LDL is present in human liver which does not efficiently modulate hepatocyte cholesterol content or synthesis.

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“…N-acetyl-D-mannosamine is a precursor for sialic acid, a protective metabolite during heat stress, and could also be produced by S. symbiotica when not under stress (sialic acid was not represented in both libraries used for metabolite identification). Mannose-6-phosphate targets newly synthesized hydrolytic enzymes to lysosomes, and its increased concentration in S. symbiotica-infected aphids in heat-shock conditions suggests its involvement in host degradation of lysed symbiont proteins (Sly and Fischer, 1982). In comparison, for all aphid genotypes, sucrose levels are not significantly altered by symbionts in control conditions.…”

Section: Symbiont Responses To Heat-shockmentioning

confidence: 93%

Effects of facultative symbionts and heat stress on the metabolome of pea aphids

2009

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We examined metabolite pools of pea aphids with different facultative symbiont infections, and characterized their effects on aphid metabolism in baseline and heat stress conditions. The bacterial symbiont Serratia symbiotica protects aphid hosts from the detrimental results of heat stress and shields the obligate symbiont Buchnera from effects of heat. We investigated whether broad effects on metabolism might correlate with this protection. Both facultative symbiont infection and heat treatment had large effects on the aphid metabolome. All three pea aphid facultative symbionts had similar effects on aphid metabolism despite their evolutionary diversity. Paradoxically, heat triggers lysis of many S. symbiotica cells and a correlated rapid reduction in S. symbiotica titres within aphid hosts. We conclude that facultative symbionts can have substantial effects on host metabolic pools, and we hypothesize that the protective effects of S. symbiotica may reflect the delivery of protective metabolites to aphid or Buchnera cells, after heat exposure.

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The Phosphomannosyl Recognition System for Intracellular and Intercellular Transport of Lysosomal Enzymes

Cited by 364 publications

References 76 publications

Intercellular trafficking of VP22-GFP fusion proteins is not observed in cultured mammalian cells

Intercellular trafficking of VP22-GFP fusion proteins is not observed in cultured mammalian cells

Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects

Effects of facultative symbionts and heat stress on the metabolome of pea aphids

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