The Insulin Receptors of Chick Embryo Show Tissue- Specific Structural Differences which Parallel those of the Insulin-Like Growth Factor I Receptors*

Abstract

Since specific binding to receptors and biological effects of insulin and insulin-like growth factors (IGFs) are demonstrable soon after the neural tube closes and organogenesis begins in the chick embryo, in the present study we have analyzed the structural characteristics and specificity of the receptors for insulin and IGFs at this early stage of development. We show that membranes from newly differentiated chick embryo tissues (day 6 brain, day 6 heart, day 8 liver, day 12 skeletal muscle) as well as whole embryos postneurulation (day 2, stage of 27-30 somites) have two populations of receptors with distinct specificity: insulin and type I IGF (IGF-I) receptors. Both insulin and IGF-I .alpha.-subunits, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, had tissue-dependent heterogeneity in Mr (liver > heart = skeletal muscle > brain) ranging from 138 kilodaltons (kDA) to 129 kDA. Desialylation of the receptors by treatment with neuraminidase produced a significant change in the Mr of the .alpha.-subunits in liver and heart but not in brain or the whole day 2 embryo. In each tissue the pattern for insulin receptors and IGF-I receptor was strikingly similar. Our studies raise the possibility that posttranslational modifications of the insulin and IGF-I receptors, characteristics of terminally differentiated tissues, are already present in early organogenesis. Further, structural heterogeneity of the binding subunit of these receptors among tissues appears to be widespread and not exclusive to the brain receptor. An insulin receptor with features similar to the neural type is the only one detected in embryos at the beginning of organogenesis (day 2). The functional implication of this developmental tissue-specific regulation of insulin and IGF-I receptors, is still speculative. Its possible importance is suggested by the fact that it occurs embryologically early and affects both insulin and IGF-I receptors in parallel.