Iron (Fe) plays an essential role in numerous metabolic processes. The transferrin receptor (TfR) is a cell membrane-associated protein that serves as a gatekeeper in regulating cellular uptake of Fe from transferrin (Tf) by TfR-mediated endocytosis. TfRs are expressed ubiquitously, but their highest levels of expression are on immature erythroid cells (which are the most avid consumers of Fe in the organism) and on rapidly dividing cells, both normal and malignant. In proliferating non-erythroid cells TfR expression is feedback inhibited by Fe through the interaction of specific binding proteins, iron regulatory proteins (IRPs), with iron responsive elements (IREs) in the 3 ' untranslated region (UTR) of TfR mRNA. However, results from our lab indicate that in differentiating murine erythroleukemia (MEL) cells, TfR expression responds only slightly to an increase in intracellular Fe. An explanation for this is lacking. Importantly, a second TfR (TfR2) has recently been cloned in humans. TfR2 is highly homologous with the classical receptor, TfR1 (except for the lack of IREs in the 3' UTR), and seems to have a similar function, but shows different tissue distribution. It has been speculated that TfR2 is expressed in erythroid cells since its message is abundant in K562 cells, a human cell line that can differentiate along an erythroid lineage, and can be induced to synthesize hemoglobin. Thus, it is important to determine whether TfR2 is expressed in erythroid cells, since this could possibly explain differences in TfR regulation in erythroid vs. non-erythroid cells. In this study, I have cloned mouse TfR2 (mTfR2) by RACE (rapid amplification of cDNA ends) and sequenced it. The sequence analysis shows approximately 50% and 82% homology to mouse TfR1 and human TfR2, respectively. Tissue distribution of mTfR2, based on Northern blot analysis indicated that, in the mouse, TfR2 mRNA was predominantly expressed in the liver and its level increased about 2 fold after a
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33861 |
| Date | January 2002 |
| Creators | Yoon, Hye-Sun Melissa, 1977- |
| Contributors | Ponka, P. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001864121, proquestno: MQ78978, Theses scanned by UMI/ProQuest. |
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