Clathrin, Adaptors, and Sorting

Pearse, B. M. F.; Robinson, Margaret S.

doi:10.1146/annurev.cb.06.110190.001055

Cited by 680 publications

(464 citation statements)

References 59 publications

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“…Membrane receptors are sorted into coated pits by a cytoplasmic internalization signal that interacts with specific assembly or adaptor proteins. 27 The finding that HFE decreases the efficiency of Tf-bound TfR endocytosis suggests that HFE can prevent TfR from clustering in coated pits. It is possible that TfR-associated proteins that are displaced by HFE (Figure 5a) are adaptor proteins and by preventing their interactions with the TfR internalization domain, HFE effectively inhibits the endocytosis of the Tf-TfR complexes via clathrin coated pits.…”

Section: Discussionmentioning

confidence: 99%

The major histocompatibility complex-encoded class I-like HFE abrogates endocytosis of transferrin receptor by inducing receptor phosphorylation

Salter–Cid¹,

Brunmark²,

Peterson³

et al. 2000

Genes Immun

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The major histocompatibility complex-encoded gene, Hfe, has been implicated to play a pivotal role in hereditary hemochromatosis, a common autosomal recessive disorder of iron metabolism. The recent finding that a physical interaction between HFE and transferrin receptor establishes a functional link between HFE and transferrin receptormediated iron metabolism in the pathophysiology of hereditary hemochromatosis. To elucidate the underlying mechanisms by which HFE interacts with and affects transferrin receptor function, we have systematically investigated the consequences of the HFE-transferrin receptor interaction in cellular iron homeostasis. Herein we show that in HFEexpressing cells, the amount of intracellular transferrin is decreased by ෂ28%, despite a ෂ40% increase in surfaceexpressed transferrin receptor. Kinetic analysis of receptor-bound transferrin endocytosis reveals that HFE expression not only reduces transferrin binding but also abrogates transferrin receptor endocytosis. As a result, HFE expression leads to an accumulation of non-functional transferrin receptors at the cell surface, and a decrease in iron uptak. Moreover, HFE expression induces hyper-serine phosphorylation of the transferrin receptor. Taken together, these results suggest that HFE negatively modulates cellular iron uptake by impairing transferrin receptor endocytosis via HFE-induced receptor phosphorylation. Genes and Immunity (2000) 1, 409-417.

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Section: Discussionmentioning

confidence: 99%

The major histocompatibility complex-encoded class I-like HFE abrogates endocytosis of transferrin receptor by inducing receptor phosphorylation

Salter–Cid¹,

Brunmark²,

Peterson³

et al. 2000

Genes Immun

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“…4A, right). Clathrin is concentrated in transport vesicles derived from the plasma membrane and the TGN (35,36) and can be used as a TGN marker (34,35), although a subpopulation of recycling endosomes also consists of clathrin-coated vesicles (37). Confocal imaging of the basal side of cells revealed that, under hypertonic conditions, whereas AQP2 (red) was concentrated at the proximity of the plasma membrane, golgin-97 (green) was predominantly perinuclear.…”

Section: Acute Hypertonicity Induces Segregation Of Ser 256 -Phosphormentioning

confidence: 99%

Acute Hypertonicity Alters Aquaporin-2 Trafficking and Induces a MAPK-dependent Accumulation at the Plasma Membrane of Renal Epithelial Cells

Hasler

Nunes²,

Bouley³

et al. 2008

Journal of Biological Chemistry

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The unique phenotype of renal medullary cells allows them to survive and functionally adapt to changes of interstitial osmolality/tonicity. We investigated the effects of acute hypertonic challenge on AQP2 (aquaporin-2) water channel trafficking. In the absence of vasopressin, hypertonicity alone induced rapid (<10 min) plasma membrane accumulation of AQP2 in rat kidney collecting duct principal cells in situ, and in several kidney epithelial lines. Confocal microscopy revealed that AQP2 also accumulated in the trans-Golgi network (TGN) following hypertonic challenge. AQP2 mutants that mimic the Ser 256 -phosphorylated and -nonphosphorylated state accumulated at the cell surface and TGN, respectively. Hypertonicity did not induce a change in cytosolic cAMP concentration, but inhibition of either calmodulin or cAMP-dependent protein kinase A activity blunted the hypertonicity-induced increase of AQP2 cell surface expression. Hypertonicity increased p38, ERK1/2, and JNK MAPK activity. Inhibiting MAPK activity abolished hypertonicity-induced accumulation of AQP2 at the cell surface but did not affect either vasopressin-dependent AQP2 trafficking or hypertonicity-induced AQP2 accumulation in the TGN. Finally, increased AQP2 cell surface expression induced by hypertonicity largely resulted from a reduction in endocytosis but not from an increase in exocytosis. These data indicate that acute hypertonicity profoundly alters AQP2 trafficking and that hypertonicity-induced AQP2 accumulation at the cell surface depends on MAP kinase activity. This may have important implications on adaptational processes governing transcellular water flux and/or cell survival under extreme conditions of hypertonicity.Most mammalian cells are exposed to an extracellular environment that remains isotonic under normal physiological conditions, largely as a result of renal regulatory mechanisms that maintain water and electrolyte body fluid composition within a very narrow range. This process relies on the countercurrent concentration mechanism that occurs along the loop of Henle and which, in turn, depends on the generation of a NaCl and urea concentration gradient along the cortico-papillary axis. As a consequence, renal medullary cells are physiologically exposed to changing conditions of variable interstitial osmolality/tonicity that can reach up to 1200 mosmol/kg in human inner medulla and up to 4500 mosmol/kg in some remarkable rodent species that are adapted to life in arid desert conditions (1). The unique phenotype of these cells allows them to survive and function under these "hostile" conditions and to rapidly adapt to recurrent variations in their environmental tonicity that follow physiological and behavioral changes. In addition to the promotion of intracellular events that ensure cell survival, hypertonicity also promotes events that mediate changes in cell function in various physiological settings. Both rapid and slow responses mediate cell adaptation to increased extracellular tonicity. Rapid responses include actin and micr...

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“…Because coated vesicles/pits usually appear as 100 -150 nm vesicles/vesicular invaginations of the plasma membrane (Pearse and Robinson, 1990) and caveolae as 50 -90 nm omega-shaped membrane invaginations Rothberg et al, 1992), we therefore defined caveolae as omegashaped invaginations of the plasma membrane less than 100 nm in the diameter in a plane of single section in the present study. Distinctive coated pits with bristles less than 100 nm in the diameter were properly excluded from that population.…”

Section: Hrp Localization In Control Endothelial Cellsmentioning

confidence: 99%

Caveolar and intercellular channels provide major transport pathways of macromolecules across vascular endothelial cells

Ogawa¹,

Imai²,

Ogawa³

et al. 2001

Anat. Rec.

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Serum macromolecules are transported through the vascular endothelial layer to the interstitium via the caveolae and interendothelial clefts, but the nature of the permeability of these structures is unknown, and the manner of caveola-vesicle transport is controversial. We have developed a method of detecting macromolecular channels using an in situ HRP perfusion into arteries previously perfused with aldehyde and random conventional sectioning for electron microscopy. Using unbiased morphometry, 4.75% of the abluminal caveolae and 15.13% of the intercellular clefts were the tracer-positive in rat aortic endothelium. In rat aortas treated with N-ethylmaleimide, all caveolae and most free vesicles in the cytoplasm except those around the Golgi area were HRP-positive in the endothelial cells; 1.48% of abluminal caveolae were structurally recognized as caveolar channels through the endothelial layer in a plane of single section. The length density of the abluminal caveolae was decreased to about 80% to the physiological control level whereas the larger invaginations were more frequently observed. Moreover 96.17% of the intercellular clefts were HRP-positive. We suggest that a flexible channel-system functions extensively as a macromolecular transport pathway in the arterial endothelium in vivo because the tracer-labeled abluminal caveolae and intercellular clefts should be opened to the luminal surfaces methodologically. We therefore propose that caveolar channels, rather than transcytosis, provide a mechanism of caveola-vesicle transport in the endothelial cells, because free vesicles involved in transcytosis were few in number. Anat Rec 264:32-42, 2001.

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Clathrin, Adaptors, and Sorting

Cited by 680 publications

References 59 publications

The major histocompatibility complex-encoded class I-like HFE abrogates endocytosis of transferrin receptor by inducing receptor phosphorylation

The major histocompatibility complex-encoded class I-like HFE abrogates endocytosis of transferrin receptor by inducing receptor phosphorylation

Acute Hypertonicity Alters Aquaporin-2 Trafficking and Induces a MAPK-dependent Accumulation at the Plasma Membrane of Renal Epithelial Cells

Caveolar and intercellular channels provide major transport pathways of macromolecules across vascular endothelial cells

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