Loss of one asparagine-linked oligosaccharide from human transferrin receptors results in specific cleavage and association with the endoplasmic reticulum.

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)

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Expression levels of human transferrin receptors in Neisseria species

Journal of Microbiological Methods ◽

10.1016/0167-7012(92)90050-e ◽

1992 ◽

Vol 15 (4) ◽

pp. 321-326 ◽

Cited By ~ 5

Author(s):

Mar Pintor ◽

Carlos Ferreirós ◽

Maria Teresa Criado ◽

Lucia Ferrón

Keyword(s):

Transferrin Receptors ◽

Expression Levels ◽

Neisseria Species ◽

Human Transferrin

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Immunotoxin sensitivity of Chinese hamster ovary cells expressing human transferrin receptors with differing internalization rates

Cancer Immunology Immunotherapy ◽

10.1007/s002620050294 ◽

1996 ◽

Vol 42 (6) ◽

pp. 357-361 ◽

Cited By ~ 8

Author(s):

L. D. Recht ◽

Vic Raso ◽

Roger Davis ◽

Rebecca Salmonsen

Keyword(s):

Chinese Hamster Ovary ◽

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Transferrin Receptors ◽

Ovary Cells ◽

Human Transferrin

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Role of oligosaccharides in the processing and function of human transferrin receptors. Effect of the loss of the three N-glycosyl oligosaccharides individually or together.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)53193-8 ◽

1993 ◽

Vol 268 (10) ◽

pp. 7435-7441

Author(s):

B. Yang ◽

M.H. Hoe ◽

P. Black ◽

R.C. Hunt

Keyword(s):

Transferrin Receptors ◽

Human Transferrin ◽

And Function

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

Biochemical Journal ◽

10.1042/bj2670031 ◽

1990 ◽

Vol 267 (1) ◽

pp. 31-35 ◽

Cited By ~ 29

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.

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In Polarized MDCK Cells Basolateral Vesicles Arise from Clathrin-γ-adaptin–coated Domains on Endosomal Tubules

The Journal of Cell Biology ◽

10.1083/jcb.141.3.611 ◽

1998 ◽

Vol 141 (3) ◽

pp. 611-623 ◽

Cited By ~ 172

Author(s):

C.E. Futter ◽

A. Gibson ◽

E.H. Allchin ◽

S. Maxwell ◽

L.J. Ruddock ◽

...

Keyword(s):

Steady State ◽

Mdck Cells ◽

Brefeldin A ◽

Transferrin Receptors ◽

Human Transferrin ◽

Asymmetric Distributions ◽

Polymeric Immunoglobulins ◽

Intracellular Mechanisms

Human transferrin receptors (TR) and receptors for polymeric immunoglobulins (pIgR) expressed in polarized MDCK cells maintain steady-state, asymmetric distributions on the separate basolateral and apical surfaces even though they are trafficking continuously into and across these cells. The intracellular mechanisms required to maintain these asymmetric distributions have not been located. Here we show that TR and pIgR internalize from both surfaces to a common interconnected endosome compartment that includes tubules with buds coated with clathrin lattices. These buds generate vesicles that carry TR to the basolateral border. The lattices contain γ-adaptin and are dispersed by treatment with brefeldin A (BFA). Since BFA treatment abrogates the vectorial trafficking of TR in polarized MDCK cells, we propose that the clathrin-coated domains of the endosome tubules contain the polarized sorting mechanism responsible for their preferential basolateral distribution.

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