Developmental expression of the IGF‐II/mannose 6‐phosphate receptor

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Abstract
The first indication that the insulin‐like growth factor‐II/mannose 6‐phosphate receptor (IGF‐II/M6PR) is developmentally regulated came from studies of the serum form of the receptor in the rat. By immunoblotting, the circulating form of the receptor, which was 10 kDa smaller than the tissue receptor, was high in 19 day fetal and 3, 10, and 20 day postnatal sera and then declined sharply. We next used quantitative immunoblotting to measure the total tissue IGF‐II/M6PR in the rat. The receptor levels were high in fetal tissues and in most tissues declined dramatically in late gestation and/or in the early postnatal period. The rank order of receptor expression was heart > placenta > lung = intestine > muscle = kidney > liver > brain. In heart, the receptor was 1.7% of total protein in the extract. More recently, we have examined the expression of IGF‐II/M6PR mRNA using Northern blotting and a solution hybridization/RNase protection assay. The rank order of receptor mRNA concentration among fetal tissues agreed with the rank order of receptor protein. The concentration of receptor mRNA was significantly lower in postnatal tissue than in fetal tissue. Thus IGF‐II/M6PR mRNA concentration is an important determinant of receptor protein in most tissues. What is the function of the IGF‐II/M6PR in embryonic and fetal tissues? The M6PR in birds and frogs does not bind IGF‐II. It is intriguing that the rat IGF‐II/M6PR is prominent during the embryonic and fetal periods, times at which the differences between mammals, on the one hand, and frogs and birds, on the other, are most striking. Tissue remodeling is an important feature of embryonic and fetal development. Therefore, the well‐established lysosomal enzyme targeting function of the receptor may be of particular importance. Since IGF‐II can inhibit the cellular uptake of lysosomal enzymes via the IGF‐II/M6PR, IGF‐II may modulate this lysosomal enzyme targeting function. In addition, the receptor can provide a degradative pathway for IGF‐II by receptor‐mediated internalization. Thus the receptor could provide a check on the high levels of IGF‐II known to be present in the fetus. Finally, the IGF‐II/M6PR could directly signal certain biologic responses to IGF‐II.

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