Preferential hepatic uptake of iron from rat asialotransferrin: possible engagement of two receptors

1986 ◽  
Vol 251 (3) ◽  
pp. G398-G404
Author(s):  
J. R. Rudolph ◽  
E. Regoeczi ◽  
P. A. Chindemi ◽  
M. T. Debanne
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
Rat Hepatocytes ◽  
Hepatic Uptake ◽  
Hepatic Iron ◽  
Transferrin Receptors ◽  
Binding Studies ◽  
Human Transferrin ◽  
Homologous Protein ◽  
Intact Rats

Hepatic iron uptake from and degradation of rat asialotransferrin prepared from the least anionic (major) component of rat transferrin were studied in intact rats. In experiments lasting 60-90 min, rat asialotransferrin delivered a three to four times larger fraction of the Fe dose to the liver than rat transferrin. Variations in the concentration of endogenous circulating rat 2Fe-transferrin by up to 300% failed to affect the enhanced hepatic delivery of Fe from rat asialotransferrin. However, pretreating the animals with a large dose of asialomucin, or fully sialylated human transferrin, or a combination of both did affect the delivery. In all cases, rat asialotransferrin delivered Fe to the liver at rates comparable with those seen with rat transferrin. The reason for the efficacy of human transferrin was clarified in competitive binding studies on rat hepatocytes and reticulocytes, which showed that human transferrin possessed an approximately sevenfold higher affinity for rat transferrin receptors than the homologous protein. These findings suggest that the enhanced hepatic uptake of Fe from rat asialotransferrin is mediated by simultaneous binding of the ligand both through its glycan and transferrin receptor affinity site. Pretreatment with asialomucin and human transferrin had no suppressing effect on basal hepatic delivery of iron from rat 2Fe-transferrin. The data suggest that deposition of a significant fraction of Fe in rat liver from rat transferrin is likely to take place by a mechanism not involving transferrin receptors. Desialylation shortened the metabolic half-life of rat transferrin from 33 to 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effect of aluminium on iron uptake and transferrin-receptor expression by human erythroleukaemia K562 cells

1990 ◽  
Vol 272 (2) ◽  
pp. 377-382 ◽  
Author(s):  
S J McGregor ◽  
M L Naves ◽  
R Oria ◽  
J K Vass ◽  
J H Brock
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
K562 Cells ◽  
Inhibitory Effect ◽  
Receptor Expression ◽  
Transferrin Receptors ◽  
High Concentration ◽  
Intracellular Release ◽  
Aluminium Citrate ◽  
Transferrin Receptor Expression

Incubation of human erythroleukaemia K562 cells with Al-transferrin inhibited iron uptake from 59Fe-transferrin by about 80%. The inhibition was greater than that produced by a similar quantity of Fe-transferrin. Preincubation of cells for 6 h with either Al-transferrin or Fe-transferrin diminished the number of surface transferrin receptors by about 40% compared with cells preincubated with apo-transferrin. Al-transferrin did not compete significantly with Fe-transferrin for transferrin receptors and, when cells were preincubated for 15 min instead of 6 h, the inhibitory effect of Al-transferrin on receptor expression was lost. Both forms of transferrin also decreased the level of transferrin receptor mRNA by about 50%, suggesting a common regulatory mechanism. Aluminium citrate had no effect on iron uptake or transferrin-receptor expression. AlCl3 also had no effect on transferrin-receptor expression, but at high concentration it caused an increase in iron uptake by an unknown, possibly non-specific, mechanism. Neither Al-transferrin nor AlCl3 caused a significant change in cell proliferation. It is proposed that aluminium, when bound to transferrin, inhibits iron uptake partly by down-regulating transferrin-receptor expression and partly by interfering with intracellular release of iron from transferrin.

scholarly journals A point mutation in the cytoplasmic domain of the transferrin receptor inhibits endocytosis

1990 ◽  
Vol 267 (1) ◽  
pp. 31-35 ◽  
Author(s):  
E Alvarez ◽  
N Gironès ◽  
R J Davis
Keyword(s):  
Transferrin Receptor ◽  
Chinese Hamster Ovary Cells ◽  
Cytoplasmic Domain ◽  
Cysteine Residue ◽  
Transferrin Receptors ◽  
Human Transferrin ◽  
Human Transferrin Receptor ◽  
Significant Difference ◽  
The Difference ◽  
Human Receptor

The rate of receptor-mediated endocytosis of diferric 125I-transferrin by Chinese-hamster ovary cells expressing human transferrin receptors was compared with the rate measured for cells expressing hamster transferrin receptors. It was observed that the rate of endocytosis of the human transferrin receptor was significantly higher than that for the hamster receptor. In order to examine the molecular basis for the difference between the observed rates of endocytosis, a cDNA clone corresponding to the cytoplasmic domain of the hamster receptor was isolated. The predicted primary sequence of the cytoplasmic domain of the hamster transferrin receptor is identical with that of the human receptor, except at position 20, where a tyrosine residue in the human sequence is replaced with a cysteine residue. To test the hypothesis that this structural change in the receptor is related to the difference in the rate of internalization, we used site-directed mutagenesis to examine the effect of the replacement of tyrosine-20 with a cysteine residue in the human transferrin receptor. It was observed that the substitution of tyrosine-20 with cysteine caused a 60% inhibition of the rate of iron accumulation by cells incubated with [59Fe]diferric transferrin. No significant difference between the rate of internalization of the mutant (cysteine-20) human receptor and the hamster receptor was observed. Thus the substitution of tyrosine-20 with a cysteine residue can account for the difference between the rate of endocytosis of the human and hamster transferrin receptors.

Expression and changing distribution of the human transferrin receptor in developing Drosophila oocytes and embryos

1996 ◽  
Vol 109 (13) ◽  
pp. 3113-3119 ◽  
Author(s):  
M.S. Bretscher
Keyword(s):  
Transferrin Receptor ◽  
Messenger Rna ◽  
Plasma Membranes ◽  
Posterior Pole ◽  
Transferrin Receptors ◽  
Human Transferrin ◽  
Human Transferrin Receptor ◽  
Cell Plasma ◽  
Cytoplasmic Vesicles ◽  
Ring Canals

In order to understand better the membrane systems in a developing Drosophila oocyte, the human transferrin receptor has been expressed there. This was achieved using the armadillo promoter combined with K10 or oskar trailer sequences; these enable the messenger RNA to be transcribed in nurse cells and then transported to, and translated in, oocytes. This is the first exogenous protein to be expressed in oocytes. At stage 8, the transferrin receptors are mainly concentrated towards the posterior pole of the oocyte and are associated with large cytoplasmic vesicles; when combined with the shibire mutation the transferrin receptors are transferred to the oolemma, demonstrating that they participate in an endocytic cycle. At stage 10, the transferrin receptors are localised either to the anterior margin of the oocyte or to the posterior pole, depending on where the mRNA is located. In newly laid eggs, all the transferrin receptors are found in large cytoplasmic vesicles. The results reveal remarkable sorting processes which occur as oocytes mature and show that ring canals, which separate the oolemma from nurse cell plasma membranes, act as barriers to prevent components in these two compartments from intermixing.

scholarly journals Transferrin receptor 1-mediated iron uptake plays an essential role in hematopoiesis

Haematologica ◽  
2019 ◽  
Vol 105 (8) ◽  
pp. 2071-2082 ◽  
Author(s):  
Shufen Wang ◽  
Xuyan He ◽  
Qian Wu ◽  
Li Jiang ◽  
Liyun Chen ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
Essential Role ◽  
Transferrin Receptor 1
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