Uptake and processing of 59Fe-labelled and 125I-labelled rat transferrin by early organogenesis rat conceptuses in vitro

Young, D M; Klemm, Ann R; Beckman, David A.; Brent, Robert L.; Lloyd, John

doi:10.1016/0143-4004(77)90010-8

Cited by 13 publications

(9 citation statements)

References 31 publications

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“…In addition to the kidney, cubilin probably also mediates uptake in the yolk sac epithelium, which is known to catabolize Tf in rodents (7). Accordingly, we measured a high cubilinmediated Tf uptake in yolk sac-derived epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the TfR-and TfR2-mediated uptake of Tf, the existence of a third receptor pathway for Tf in some polarized epithelia seems likely. One important line of evidence for this comes from studies by Young et al (7), who have shown that Tf is effectively endocytosed from the luminal (apical) surfaces of polarized yolk sac cells despite the basolateral membrane sorting of TfR in polarized epithelia (8,9). Another line of evidence comes from the fact that the uptake of Tf in the yolk sac (7) and other organs such as the kidney (10) leads to catabolism of Tf.…”

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confidence: 96%

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Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia

Kozyraki

Fyfe

Verroust

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

245

211

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Cubilin is a 460-kDa protein functioning as an endocytic receptor for intrinsic factor vitamin B 12 complex in the intestine and as a receptor for apolipoprotein A1 and albumin reabsorption in the kidney proximal tubules and the yolk sac. In the present study, we report the identification of cubilin as a novel transferrin (Tf) receptor involved in catabolism of Tf. Consistent with a cubilinmediated endocytosis of Tf in the kidney, lysosomes of human, dog, and mouse renal proximal tubules strongly accumulate Tf, whereas no Tf is detectable in the endocytic apparatus of the renal tubule epithelium of dogs with deficient surface expression of cubilin. As a consequence, these dogs excrete increased amounts of Tf in the urine. Mice with deficient synthesis of megalin, the putative coreceptor colocalizing with cubilin, also excrete high amounts of Tf and fail to internalize Tf in their proximal tubules. However, in contrast to the dogs with the defective cubilin expression, the megalin-deficient mice accumulate Tf on the luminal cubilin-expressing surface of the proximal tubule epithelium. This observation indicates that megalin deficiency causes failure in internalization of the cubilin-ligand complex. The megalin-dependent, cubilin-mediated endocytosis of Tf and the potential of the receptors thereby to facilitate iron uptake were further confirmed by analyzing the uptake of 125 I-and 59 Fe-labeled Tf in cultured yolk sac cells.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia

Kozyraki

Fyfe

Verroust

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

245

211

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“…Finally, the next series of experiments indicated that receptor‐mediated endocytosis is also responsible for the delivery of certain vitamins to the developing embryo (Lloyd et al,1998). For example, absorption of vitamin B12 and iron are achieved by receptor‐mediated endocytosis of intrinsic factor/transcobalamin‐bound vitamin B12 and transferrin‐bound iron, respectively (Moestrup et al,1996; Young et al,1997).…”

Section: Introductionmentioning

confidence: 99%

“…Uptake by transferrin receptors results in unloading of iron in the endosome and recycling of apo‐transferrin and the receptor to the basal cell surface (Dautry‐Varsat et al,1983). In the VE of the yolk sac, however, transferrin receptors are localized primarily to the basal side of the endodermal cells of the VYS (Young et al,1997). Furthermore, uptake of iron‐bound transferrin occurs on the apical side of the VYS endoderm cell and results in catabolism of transferrin (Young et al,1997).…”

Section: Introductionmentioning

confidence: 99%

“…In the VE of the yolk sac, however, transferrin receptors are localized primarily to the basal side of the endodermal cells of the VYS (Young et al,1997). Furthermore, uptake of iron‐bound transferrin occurs on the apical side of the VYS endoderm cell and results in catabolism of transferrin (Young et al,1997). Because of these inconsistencies, it has been hypothesized that the multiligand endocytic receptor complex likely plays a major role in the uptake of iron on the apical surface of VYS endoderm (Kozyraki et al,2001).…”

Section: Introductionmentioning

confidence: 99%

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The visceral yolk sac endoderm provides for absorption of nutrients to the embryo during neurulation

Zohn

Sarkar

2010

Birth Defects Research

100

113

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Neural tube defects (NTDs) represent some of the most common congenital malformations in humans. The causes of NTDs are complex with both genetic and environmental contributing factors. Periconception nutrition is an important environmental factor influencing the penetrance of NTDs. NTDs arise from failure to close the neural tube completely during development, an event that occurs before establishment of the chorioallantoic placenta. During neurulation, nutrients are absorbed by histotrophic mechanisms and absorbed by endocytosis in the endoderm-derived cell layer of the visceral yolk sac (VYS). Here we review the histotrophic mechanisms by which nutrients are delivered to the human embryo during this critical time period. Because more detailed studies on the molecular mechanisms regulating uptake of nutrients have been performed using rodent models, most importantly mouse and rat models, we will also review nutrient uptake in these model organisms to set the stage for presentation of experimental data that have provided valuable information about how nutrients are delivered to the neurulating embryo.

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Is low iron status a risk factor for neural tube defects?

Molloy

Einri

Jain

et al. 2014

Birth Defects Research

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Background Folic acid supplements can protect against neural tube defects (NTDs). Low folate and low vitamin B12 status may be maternal risk factors for having an NTD affected pregnancy. However, not all NTDs are preventable by having an adequate folate/ B12 status and other potentially modifiable factors may be involved. Folate and vitamin B12 status have important links to iron metabolism. Animal studies support an association between poor iron status and NTDs but human data are scarce. We examined the relevance of low iron status in a nested NTD case-control study of women within a pregnant population-based cohort. Methods Pregnant women were recruited between 1986 and 1990, when vitamin or iron supplementation in early pregnancy was rare. Blood samples, taken at an average of 14 weeks gestation, were used to measure ferritin and hemoglobin in 64 women during an NTD affected pregnancy and 207 women with unaffected pregnancies. Results No significant differences in maternal ferritin or hemoglobin concentrations were observed between NTD affected and non-affected pregnancies (case median ferritin 16.8μg/L and hemoglobin 12.4g/dL versus 15.4μg/L and 12.3g/dL in controls). As reported previously, red cell folate and vitamin B12 concentrations were significantly lower in cases. Furthermore, there was no significant association of iron status with type of NTD lesion (anencephaly or spina bifida) Conclusions We conclude that low maternal iron status during early pregnancy is not an independent risk factor for NTDs. Adding iron to folic acid for periconceptional use may improve iron status but is not likely to prevent NTDs.

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Uptake and processing of 59Fe-labelled and 125I-labelled rat transferrin by early organogenesis rat conceptuses in vitro

Cited by 13 publications

References 31 publications

Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia

Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia

The visceral yolk sac endoderm provides for absorption of nutrients to the embryo during neurulation

Is low iron status a risk factor for neural tube defects?

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