Characterization of a novel form of transferrin receptor preferentially expressed on normal erythroid progenitors and precursors

Abstract

A panel of monoclonal antibodies (MoAbs) against cell surface proteins of early BFUe progeny was characterized. Five of these antibodies (Abs) reacted with normal erythroid, but not myeloid, bone marrow cells. Each of the five antibodies, typified by Ab 69.20, immunoprecipitated a dimeric complex of 185,000, which is composed of two identical disulfide-bonded subunits. This antigen had affinity for transferrin, and was essentially identical in biochemical characteristics to transferrin receptors precipitated with the well-characterized MoAbs OKT9 and 5E9. However, this form of transferrin receptor lacked both the OKT9 and 5E9 antigenic determinants and, moreover, the 69.20 epitope was absent from the conventional transferrin receptor, as defined by Abs OKT9 and 5E9. Modulation experiments demonstrated that both 69.20 and OKT9 modulated large, virtually independent populations of transferrin receptors. Both forms of transferrin receptor appeared to be derived from the product of a single gene, but the form defined by MoAb 69.20 apparently predominates in cells of the erythroid lineage and some transformed cell types that manifest a special requirement for iron. These data suggest that cells with a high iron requirement synthesize two forms of transferrin receptor, possibly by means of differential mRNA splicing or by posttranslational modification of the transferrin receptor.

Expression of signal transduction proteins during the differentiation of primary human erythroblasts

“…The fact that high levels of glycophorin A (recognized by the CD235a antibody) (Robinson et al, 1981) and of the transferrin receptor I (recognized by CD71) (Iacopetta et al, 1982; Sawyer and Krantz, 1986) expression also occur during the maturation of human erythroblasts has inspired a citofluorimetric definition of human cells according to the same principle used for the mouse (Wojda et al, 2003). However, in humans the increased iron requirement associated with the progression of erythroid maturation is met not only by increasing the expression of the transferrin receptor I, but also by activating the expression of an erythroid‐specific receptor isoform (Cotner et al, 1989) encoded by the transferrin receptor 2 gene (Kawabata et al, 1999). Preliminary experiments had indicated that erythroid differentiation was associated with a pattern of CD71 expression similar to that observed in the mouse in only 40% of the donor population to whom we had access (data not shown).…”

Receptor‐mediated iron uptake and intracellular iron transport

“…It is now clear that the intracellular processing of transferrin to effect iron release involves more than one pathway, as demonstrated by kinetic studies [12,52] and by the effect of toxins [53-551. The number (more than one, but how many more is not clear) and the functional significance of the separate pathways and whether they involve the receptor [56], the handling of iron in the endocytic vesicle, or its transit through the cytosol and uptake by mitochondria--or some combination of these-remains to be elucidated. A diagram summarizing the classic scheme and some of the changes that need to be included in a revised scheme is shown in Figure 1.…”

Η Συμβολή Των Καλλιεργειών Αιμοποιητικών Κυττάρων Στη Μελέτη Της Αναιμίας Της Χρόνιας Νεφρικής Ανεπάρκειας

“…Ένα χαρακτηριστικό των προγονικών κυττάρων μόνο της ερυθράς σειράς είναι η εν αφθονία παρουσία υποδοχέων τρανσφαιρίνης που είναι απαραίτητοι για τη μεταφορά σιδήρου και τη σύνθεση της αιμοσφαιρίνης. Η μέγιστη έκφραση των υποδοχέων αυτών απαντά στο στάδιο των CFU-E και των προδρόμων κυττάρων της ερυθράς σειράς (προερυθροβλαστών), ενώ στα δικτυοερυθροκύτταρα ανευρίσκονται σε μικρότερο βαθμό (Cotner 1989, Sawyer 1996, Ponka 1997…”