Iron is taken into proliferating cells via a high affinity receptor for the serum iron carrying protein transferrin. The transferrin receptor in a human erythroleukemia cell line is being studied as an integral membrane protein whose synthesis, degradation, and dynamics are highly regulated. The expression of the transferrin receptor has been shown to be modulated by the availability of iron in that provision of iron to the cells results in decreased receptor expression whereas chelation of intracellular iron causes augmented expression. The mechanism underlying these phenomena has been investigated by comparing directly the rates of biosynthesis and degradation of the transferrin receptor under conditions of varied iron availability. These studies indicated that receptor expression is modulated by alterations in the rate of biosynthesis by the receptor. Using a cDNA probe for the receptor, it was found that changes in biosynthetic rate are a reflection of altered levels of receptor mRNA. In vitro transcription experiments with isolated nuclei showed that the receptor mRNA is more actively transcribed in nuclei from iron depleted cells than in those from cells grown in an efficient iron source. Monoclonal antibodies to the transferrin receptor also modulate receptor expression. The effect of the antibodies on receptor degradation biosynthesis and dynamics have been investigated. It was found that exposure of cells to anti-receptor monoclonal antibodies results in a rapid redistribution of cellular transferrin receptors such that a lower percentage are expressed on the cell surface. This treatment also leads to enhanced degradation of the receptor and a resultant alteration in receptor biosynthesis that is due to iron deprivation.
