Isolation and characterization of multivesicular bodies from rat hepatocytes: an organelle distinct from secretory vesicles of the Golgi apparatus.

Hornick, Conrad A.; Hamilton, Robert L.; Spaziani, Eugene; Enders, Greg H.; Havel, Richard J.

doi:10.1083/jcb.100.5.1558

Cited by 97 publications

(41 citation statements)

References 72 publications

(89 reference statements)

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“…Cholesterol is also implicated in MVB biogenesis owing to its significant enrichment in MVBs (Hornick et al 1985). Analysis of exosomes reveals that much of the endosomal cholesterol resides in ILVs , Wubbolts et al 2003, although the levels of cholesterol within intralumenal membranes vary among cell types (Subra et al 2006).…”

Section: Machinery Lipid Sortingmentioning

confidence: 99%

Biogenesis and Function of Multivesicular Bodies

Piper

Katzmann

2007

Annu. Rev. Cell Dev. Biol.

660

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The two major cellular sites for membrane protein degradation are the proteasome and the lysosome. Ubiquitin attachment is a sorting signal for both degradation routes. For lysosomal degradation, ubiquitination triggers the sorting of cargo proteins into the lumen of late endosomal multivesicular bodies (MVBs)/endosomes. MVB formation occurs when a portion of the limiting membrane of an endosome invaginates and buds into its own lumen. Intralumenal vesicles are degraded when MVBs fuse to lysosomes. The proper delivery of proteins to the MVB interior relies on specific ubiquitination of cargo, recognition and sorting of ubiquitinated cargo to endosomal subdomains, and the formation and scission of cargo-filled intralumenal vesicles. Over the past five years, a number of proteins that may directly participate in these aspects of MVB function and biogenesis have been identified. However, major questions remain as to exactly what these proteins do at the molecular level and how they may accomplish these tasks.

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Section: Machinery Lipid Sortingmentioning

confidence: 99%

Biogenesis and Function of Multivesicular Bodies

Piper

Katzmann

2007

Annu. Rev. Cell Dev. Biol.

660

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“…Similar particles observed in prelysosomal organelles of rat liver have been identified as remnants of TG-rich lipoproteins. 32 Compositional analysis of A-VLDL isolated from aortic tissue containing mild fatty streaks showed a lower TG-tocholesterol ratio (0.57) than plasma VLDL (4.35), and SDS gradient gel bands corresponding to apo A-I, apo B-100, and C apolipoproteins were seen (Fig 3A). We observed that the VLDL fraction isolated from aortic tissue having advanced lesions contained numerous large, aggregate, lipid particles in addition to VLDLlike particles, and these VLDL-density particles contained numerous unidentified protein bands in addition to identifiable A-I and C apoproteins (data not shown).…”

Section: Characterization Of Lipoprotein-like Particles From Human Plmentioning

confidence: 99%

Liposome-like particles isolated from human atherosclerotic plaques are structurally and compositionally similar to surface remnants of triglyceride-rich lipoproteins.

Chung¹,

Tallis²,

Yalamoori³

et al. 1994

Arterioscler Thromb

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Recent studies have demonstrated the presence of unesterified cholesterol-rich, liposome-like vesicles in the extracellular space of atherosclerotic lesions in humans and animals. Liposome-like vesicles accumulate in the subendothelial space in rabbits within 2 weeks of initiation of cholesterol feeding, well before foam cells appear. These observations suggest that extracellular liposome-like vesicles may play a pivotal role in atherogenesis. The origin of these particles is unknown. We report a combination of in vivo and in vitro experiments that suggest a novel origin for these liposome-like vesicles. We demonstrate that the liposome-like particles isolated from postmortem human atherosclerotic plaques are rich in intact apolipoprotein (apo) A-I, C apolipoproteins, and sphingomyelin. We show that the in vivo derived particles are virtually identical, structurally and compositionally, to liposome-like lipolytic surface remnants of triglyceride (TG)-rich lipoproteins produced during in vitro lipolysis of hypertriglyceridemic serum. In vitro lipolysis of isolated very-low-density lipoprotein has shown that the lipolytic surface remnants remain attached to the core remnants in the absence of high-density lipoprotein (HDL), dissociate to form liposomelike vesicles in the presence of low levels of HDL, and are assimilated into HDL to form larger HDL particles in the presence of excess HDL. Thus, the in vitro produced, liposome-like particles represent a complex of lipolytic surface C holesterol deposition in the arterial intima is characteristic of human atherosclerotic plaques. 1 These deposits represent both intracellular lipid droplets (foam cells) and extracellular lipid particles. The cholesterol deposits in fibrous plaques are predominantly extracellular. 2Several recent studies have shown that atherosclerotic lesions in both humans and experimental animals contain numerous large, extracellular, liposome-like particles, which differ from extracellular spheroidal very-low-density lipoprotein (VLDL)-and low-density lipoprotein (LDL)-like particles and intracellular lipid droplets in foam cells with respect to size and chemical composition. 310 In animal models these particles accumulate before foam cells appear, emphasizing the primacy of these particles in atherogenesis.

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“…82 This was followed by studies showing the same cellular itinerary for remnants of chylomicrons and VLDL in normal as well as estradioltreated rats 83 and by the isolation and characterization of early and late endosomes and a receptor-recycling compartment from rat livers. 63,84 This work showed clearly that LDL and chylomicron and VLDL-remnants follow a common postendocytic pathway leading to lysosomal catabolism in hepatocytes.I also initiated studies of hepatic lipoprotein catabolism in Watanabe hereditary hyperlipidemic (WHHL) rabbits, homozygous for a mutant LDL receptor that is receptornegative for LDL (but not definitively for cholesterol-rich VLDL containing apoE). These animals are, however, hypertriglyceridemic as well as hypercholesterolemic and we found, together with Brown and Goldstein, that their VLDL (containing apoB-100 and rich in apoE), resemble remnant particles.…”

mentioning

confidence: 99%

Triglyceride-Rich Lipoproteins and Plasma Lipid Transport

Havel

2010

ATVB

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Abstract-This memoir provides a history of the triglyceride-rich lipoproteins of blood plasma over the last half-century.As precursors of low-density lipoproteins and in their own right, triglyceride-rich lipoproteins are essential to the formation of atherosclerotic plaques and to consequent ischemic vascular disease. The author recounts research at the National Heart Institute during 1953 to 1956 and continuing thereafter at the University of California San Francisco. Emphasis is placed on key insights arising from investigations of human disease, the interplay of fatty acid and triglyceride-transport involving the liver, small intestine, adipose tissue and muscle, and the role of the liver in the synthesis and catabolism of atherogenic lipoproteins. (Arterioscler Thromb Vasc Biol. 2010;30:9-19.)Key Words: chylomicrons Ⅲ very low-density lipoproteins Ⅲ apolipoproteins Ⅲ lipoprotein receptors Ⅲ atherosclerosis I n 1951, I was one of 8 residents at East Coast medical schools recruited by James Shannon to the National Heart Institute as Clinical Associates to provide care for patients in the Clinical Center of the National Institutes of Health (NIH). At the time, many house officers were being drafted into the U.S. Army for service in Korea. To obviate loss to a "mash" unit, we immediately joined the U.S. Public Health Service. Owing to delays in opening the Clinical Center, I was able to finish my residency at New York Hospital/Cornell Medical Center, arriving in Bethesda in 1953, where by chance I admitted the first inpatient on July 1. In addition to caring for patients our group was expected to engage in research. We were advised to "look around" and select a basic science laboratory to join. During planning for the Clinical Center, Shannon, aware that virtually no NHI scientists were doing "heart" research, asked laboratory heads to suggest appropriate disease-related areas. Christian B. Anfinsen, a protein chemist (and later Nobel laureate for his work on proteinfolding), perused the literature and suggested two topics related to plasma lipids. The first was to investigate the lipemia "clearing factor." At the University of Rochester, Paul Hahn had made a serendipitous observation: in dogs given intravenous heparin, the opalescence of blood plasma occurring postprandially rapidly disappeared. 1 Anfinsen suspected that a protein might be released into the blood by heparin. The second was to investigate the plasma lipoproteins recently described by John Gofman and his students at the University of California Berkeley. They discovered that lipoproteins can be separated from serum by ultracentrifugation and quantified in an analytic ultracentrifuge; and they had reported that a low-density group of these giant macromolecules are risk markers for coronary heart disease. 2 As a result, Anfinsen was asked to organize a new Section in the Laboratory of Metabolism in 1951. Of the 8 who arrived in 1953, Donald Fredrickson, Robert Gordon, and I joined this Section. Research at the National Heart Institute (1953 to 19...

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Isolation and characterization of multivesicular bodies from rat hepatocytes: an organelle distinct from secretory vesicles of the Golgi apparatus.

Cited by 97 publications

References 72 publications

Biogenesis and Function of Multivesicular Bodies

Biogenesis and Function of Multivesicular Bodies

Liposome-like particles isolated from human atherosclerotic plaques are structurally and compositionally similar to surface remnants of triglyceride-rich lipoproteins.

Triglyceride-Rich Lipoproteins and Plasma Lipid Transport

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