Endosomes

Helenius, Ari; Mellman, Ira; Wall, Doris A.; Hubbard, Ann L.

doi:10.1016/0968-0004(83)90350-x

Cited by 563 publications

(371 citation statements)

References 22 publications

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“…The endosomes that we describe are similar, if not identical, to those previously identified in other cell types (2,9,24,33). Early endosomes have also been termed "peripheral endosomes" due to their frequent localization near the cell surface.…”

Section: Discussionsupporting

confidence: 51%

“…Low density lipoprotein (LDL) and ct2M need only mildly acidic conditions (pH 6.5-6.7) to dissociate from their receptors (1, 17), whereas lysosomal enzyme dissociation (8), iron release (3,15,26), and penetration of diphtheria toxin (5, 31) all require a pH of <6.0. Therefore, measuring the pH of a specific type of endosome may help elucidate the role that endocytic compartment has in a particular physiologic process.From kinetic studies (12,29,32,40) it is not clear whether 9 The Rockefeller University Press, 0021-9525/87/12/2723/11 $2.00 …”

mentioning

confidence: 99%

“…From kinetic studies (12,29,32,40) it is not clear whether 9 The Rockefeller University Press, 0021-9525/87/12/2723/11 $2.00…”

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confidence: 99%

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Acidification of morphologically distinct endosomes in mutant and wild-type Chinese hamster ovary cells.

Yamashiro

Maxfield

1987

The Journal of Cell Biology

114

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we have shown that there is rapid acidification of endosomal compartments to pH 6.3 by 3 min in wildtype Chinese hamster ovary (CHO) cells. In contrast, early acidification of endosomes is markedly reduced in the CHO mutants, DTF 1-5-4 and DTF 1-5-1. Since these CHO mutants are pleiotropically defective in endocytosis (Robbins, A. R., S. S. Peng, and J. L. Marshall. 1983. J. Cell Biol. 96:1064-1071; Robbins, A. R., C. Oliver, J. L. Bateman, S. S. Krag, C. J. Galloway, and I. Mellman. 1984. J. Cell Biol. 99" 1296-1308, our results are consistent with a requirement for proper acidification of early endocytic compartments in many pH-regulated endocytic processes. In this paper, by measuring the pH of morphologically distinct endosomes using fluorescence microscopy and digital image analysis, we have determined in which of the endocytic compartments the defective acidification occurs. We found that the acidification of both the para-Golgi recycling endosomes and lysosomes was normal in the CHO mutants DTG 1-5-4 and DTF 1-5-1. The mean pH of large endosomes containing either fluorescein-labeled r or fluorescein-isothiocyanate dextran was only slightly less acidic in the mutant cells than in wild-type cells. However, when we examined the pH of individual large (150-250 nm) endosomes, we found that there was an increased number of endosomes with a pH >6.5 in the CHO mutants when compared with wildtype cells. Heterogeneity in the acidification of large endosomes was also seen in DTF 1-5-1 by a combined null point pH method and digital image analysis technique. In addition, both CHO mutants showed a marked decrease in the acidification of the earliest endosomal compartment, a diffusely fluorescent compartment comprised of small vesicles and tubules. We suggest that the defect in endosome acidification is most pronounced in the early, small vesicular, and tubular endosomes and that this defect partially carries over to the large endosomes that are involved in the sorting and processing of ligands. The proper step-wise acidification of the different endosomes along the endocytic pathway may have an important role in the regulation of endocytic processes.I N the preceding paper (40) we examined the kinetics of endosome acidification in wild-type and mutant Chinese hamster ovary (CHO) cells. We found in wild-type cells that there was a rapid (3-5 min) acidification of endosomes to pH 6.2-6.3. With time, ct~-macroglobulin (a2M) ~ and fluorescein-isothiocyanate dextran (F-Dex), molecules that are routed to lysosomes, are found in progressively more acidic endocytic compartments (pH < 6.0), while transferrin Dr. Maxfieid's present address is Departments of Pathology and Physiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.1. Abbreviations used in this paper: a2M, u2-macroglobulin; a2M-gold, a2-macroglobulin adsorbed to colloidal gold; AA/MA, ammonium acetate/methylamine; F-a2M, fluorescein-labeled ct2-macroglobulin; F-Dex, fluorescein isothioeyanate dextran; F-Tf, fluorescein-labeled transferr...

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Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 99%

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Acidification of morphologically distinct endosomes in mutant and wild-type Chinese hamster ovary cells.

Yamashiro

Maxfield

1987

The Journal of Cell Biology

114

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“…They are first concentrated in an intermediate compartment, called endosomes, where the ligand is in some cases dissociated from the receptor by low pH. The ligand is then carried to lysosomes, eventually degraded, and excreted by exocytosis, while the receptor may be recycled to the plasma membrane up to 100 times (Hopkins, 1980;Brown et al, 1983;Helenius et al, 1983;Pastan & Willingham, 1983;Rothman & Lenard, 1984). Alternatively, in the case of acid-stable receptor-ligand interactions, the receptor may be processed to lysosomes and be degraded together with the ligand, resulting in down-regulation of cell-surface receptors (Rothman & Lenard, 1984).…”

Section: Receptor Recyclingmentioning

confidence: 99%

The receptor function of the Na+, K+-activated adenosine triphosphatase system

Anner¹

1985

Biochemical Journal

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“…Like most, if not all of them, galactose-exposing derivatives are internalized through coated pits/coated vesicles and rapidly found in various electron-lucent smooth-membrane structures prior to delivery to lysosomes, where ligand degradation is initiated [3 -71. The various 'intermediate' or 'prelysosomal' organelles are referred to as a whole as endosomes [8], receptosomes [9] or CURL, an acronym for Compartment of Uncoupling of Receptors and ligands [lo]. However, the intermediate compartment appears heterogeneous, with respect to physical [I 1, 121, or morphological and topological properties [ …”

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Receptor-mediated endocytosis of polymeric IgA and galactosylated serum albumin in rat liver. Evidence for intracellular ligand sorting and identification of distinct endosomal compartments

et al. 1985

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Rat polymeric IgA (pIgA) and galactosylated bovine serum albumin (GalBSA), once injected to rats, are avidly taken up by hepatocytes via receptor‐mediated endocytosis. Of injected pIgA, 64% was transferred undigested into bile within 3 h, with a peak at 30–45 min. GalBSA was essentially digested in lysosomes. By electron microscopy using ligand‐peroxidase conjugates, both ligands were internalized through coated pits/coated vesicles into similar electron‐lucent vesicles and tubules. Subsequently, pIgA remained mostly associated with small vesicles clustering around and fusing with bile canaliculi, while GalBSA was predominantly found in large, heterogeneous endocytic structures and in lysosomes. By subcellular fractionation, they were associated at 3 min after injection with structures that similarly sedimented in the P fraction (250000−3 · 106×g×min) and equilibrated at densities of about 1.13 g/ml in sucrose gradients. At 10 min and 20 min, pIgA distribution remained mostly in the P fraction at the same equilibrium density. A minor component of the pIgA distribution was found at the density of lysosomes, but contrary to lysosomal enzymes, its distribution was not affected by Triton WR 1339. In contrast to pIgA, GalBSA was progressively recovered in the L fraction (33000−250 000 × g × min) with organelles equilibrating around 1.11 g/ml, and, by 20–45 min, was found in the ML fraction (10 000−250 000 × g × min), around 1.20 g/ml, i. e. in lysosomes. Chloroquine did not reduce the efficiency but delayed the secretion of pIgA into bile. Similarly, it did not affect the uptake of GalBSA but apparently delayed GalBSA transfer along successive populations of host organelles. The low density, GalBSA‐containing structures were devoid of proteolytic activity. Anti‐secretory component IgG and F(ab′)2 were selectively excreted into bile, partially or totally as compounds of lower molecular mass. These antibody fragments probably result from a disulfide reduction activity along the pIgA pathway. In conclusion, our data (a) strongly suggest that pIgA and GalBSA are sorted between 3 min and 10 min after injection in non‐lysosomal acidic organelles, (b) identify two successive and physically distinct endosomal populations containing GalBSA, and (c) provide the first evidence for a disulfide reduction activity along the transcytotic pathway of rat hepatocytes.

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Endosomes

Cited by 563 publications

References 22 publications

Acidification of morphologically distinct endosomes in mutant and wild-type Chinese hamster ovary cells.

Acidification of morphologically distinct endosomes in mutant and wild-type Chinese hamster ovary cells.

The receptor function of the Na+, K+-activated adenosine triphosphatase system

Receptor-mediated endocytosis of polymeric IgA and galactosylated serum albumin in rat liver. Evidence for intracellular ligand sorting and identification of distinct endosomal compartments

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