Intracellular interactions of transferrin and its receptor during biosynthesis.

Neefjes, Jacques; Hengeveld, Trudi; Tol, Olga; Ploegh, Hidde L.

doi:10.1083/jcb.111.4.1383

Cited by 13 publications

(11 citation statements)

References 37 publications

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“…An early event in the activation of IRE1a is dimerization and oligomerization (28), which is required for the activation of the kinase domain. IRE1a activation shares these features with many other trans-membrane receptors (29)(30)(31). In addition to the biochemical evidence for oligomerization, live cell microscopy with IRE1a tagged with fluorescent proteins shows it to cluster in the ER membrane in response to ER stress (13,19,(32)(33)(34).…”

mentioning

confidence: 83%

Clustering of IRE1α depends on sensing ER stress but not on its RNase activity

et al. 2019

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The sensors of the unfolded protein response react to endoplasmic reticulum (ER) stress by transient activation of their enzymatic activities, which initiate various signaling cascades. In addition, the sensor IRE1α exhibits stress‐induced clustering in a transient time frame similar to activation of its endoRNase activity. Previous work had suggested that the clustering response and RNase activity of IRE1α are functionally linked, but here we show that they are independent of each other and have different behaviors and modes of activation. Although both clustering and the RNase activity are responsive to luminal stress conditions and to depletion of the ER chaperone binding protein, RNase‐inactive IRE1α still clusters and, conversely, full RNase activity can be accomplished without clustering. The clusters formed by RNase‐inactive IRE1α are much larger and persist longer than those induced by ER stress. Clustering requires autophosphorylation, and an IRE1α mutant whose RNase domain is responsive to ligands that bind the kinase domain forms yet a third type of stress‐independent cluster, with distinct physical properties and half‐lives. These data suggest that IRE1α clustering can follow distinct pathways upon activation of the sensor.—Ricci, D., Marrocco, I., Blumenthal, D., Dibos, M., Eletto, D., Vargas, J., Boyle, S., Iwamoto, Y., Chomistek, S., Paton, J. C., Paton, A. W., Argon, Y. Clustering of IRE1α depends on sensing ER stress but not on its RNase activity. FASEB J. 33, 9811–9827 (2019). http://www.fasebj.org

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confidence: 83%

Clustering of IRE1α depends on sensing ER stress but not on its RNase activity

et al. 2019

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“…It then binds to the transferrin receptor (Neefjes et al, 1990). The dissociation of transferrin from its receptor would require the transit of the complex through an acidic compartment in order to detach iron from the protein and decrease its affinity for the receptor.…”

Section: Hypothetical Mechanismmentioning

confidence: 99%

“…Recently, it has been reported that in Hep G2 human hepatoma cells, (apo)transferrin, and transferrin receptor are synthesized and that within the endoplasmic reticulum and/or the trans-Golgi network, apotransferrin is loaded with iron. It then binds to the transferrin receptor (Neefjes et al, 1990). The dissociation of transferrin from its receptor would require the transit of the complex through an acidic compartment in order to detach iron from the protein and decrease its affinity for the receptor.…”

Section: Hypothetical Mechanismmentioning

confidence: 99%

Iron absorption by CaCo 2 cells cultivated in serum‐free medium as in vitro model of the human intestinal epithelial barrier

Halleux

Schneider

1994

Journal Cellular Physiology

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A cell culture system consisting of confluent monolayer of human enterocyte-like CaCo 2 cells, cultivated in a serum-free nutritive medium, on microporous synthetic membranes has been used as an in vitro model of the intestinal epithelial barrier. The uptake of 55ferric citrate, as well as the transepithelial passage from the apical to the basolateral pole, have been studied. CaCo 2 cells accumulate iron in a time- and concentration-dependent process, largely specific from the apical pole. When 55ferric citrate is added at the apical pole, radioiron appears at the basal pole and the clearance rate is approximately four times higher than in the opposite direction; the amounts of 55Fe increase with the concentration in iron citrate and the duration of incubation. At least two concurrent mechanisms could be involved in iron absorption across monolayers of CaCo 2 cells. A first route would correspond to a paracellular passage of the metal from the apical to the basal pole. The second route would involve a selective intake of iron at the apical pole and could require a reduction of ferric iron, prior to the entry. Iron accumulated by the cells would, for a minor part, be stored within ferritin, whereas the major part would be excreted at the basolateral pole, either as low molecular weight material of undetermined chemical composition but from which iron is easily mobilized by apotransferrin or associated with neosynthesized apotransferrin. Vesicular transport and protein synthesis seem to be required.

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“…To determine the position of ER in the gradient, PNS fractions prepared from SFV-C/TRA2-infected ceils that had been pulselabeled for 10 min and chased for 5 min were analyzed on the gradient and the radioactively labeled TRA2 was used as a marker for ER. The position of plasma membrane in the gradient was determined by analyzing PNS prepared from SFV-C/TRA2-infected cells that had been pulse-labeled for 20 min and chased for 3 h, and the slower migrating form of TRA2 (38,53) was used as a marker for the plasma membrane. Galactosyl transferase activity, a marker for trans-Golgi, was assayed in the gradient fractions as described in Brew et al (4).…”

Section: Subcellular Fractionationmentioning

confidence: 99%

Targeting of Moloney murine leukemia virus gag precursor to the site of virus budding.

Suomalainen

Hultenby

Garoff

1996

The Journal of Cell Biology

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Abstract. Retrovirus Moloney murine leukemia virus(M-MuLV) matures by budding at the cell surface. Central to the budding process is the myristoylated viral core protein precursor Gag which, even in the absence of all other viral components, is capable of associating with the cytoplasmic leaflet of the plasma membrane and assembling into extracellular virus-like particles. In this paper we have used heterologous, Semliki Forest virus-driven, expression of M-MuLV Gag to study the mechanism by which this protein is targeted to the cell surface. In pulse-chase experiments, BFA, monensin, and 20°C block did not affect incorporation of Gag into extracellular particles thereby indicating that the secretory pathway is not involved in targeting of Gag to the cell surface. Subcellular fractionation studies demonstrated that newly synthesized Gag became rapidly and efficiently associated with membranes which had a density similar to that of plasma membrane-derived vesicles. Protease-protection studies confirmed that the Gag-containing membranes were of plasma membrane origin, since in crude cell homogenates, the bulk of newly synthesized Gag was protease-resistant as expected of a protein that binds to the cytoplasmic leaflet of the plasma membrane. Taken together these data indicate that targeting of M-MuLV Gag to the cell surface proceeds via direct insertion of the protein to the cytoplasmic side of the plasma membrane. Furthermore, since the membrane insertion reaction is highly efficient and specific, this suggests that the reaction is dependent on as-yet-unidentified cellular factors.

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Intracellular interactions of transferrin and its receptor during biosynthesis.

Cited by 13 publications

References 37 publications

Clustering of IRE1α depends on sensing ER stress but not on its RNase activity

Clustering of IRE1α depends on sensing ER stress but not on its RNase activity

Iron absorption by CaCo 2 cells cultivated in serum‐free medium as in vitro model of the human intestinal epithelial barrier

Targeting of Moloney murine leukemia virus gag precursor to the site of virus budding.

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