INSULIN-LIKE GROWTH-FACTOR-I RECEPTORS OF FETAL BRAIN ARE ENRICHED IN NERVE GROWTH CONES AND CONTAIN A BETA-SUBUNIT VARIANT

Nerve growth cones isolated from fetal rat brain are highly enriched in a 97-kDa glycoprotein, termed beta(gc), that comigrates with the beta subunit of the IGF-I receptor upon two-dimensional PAGE and is disulfide-linked to this receptor's ct subunit. Antibodies prepared to a conserved domain shared by the insulin and IGF-I receptor beta submits (AbP2) or to beta(gc) were used to study receptor distribution further, Subcellular fractionation of the fetal brain segregated most AbP2 immunoreactivity away from growth cones, whereas most beta(gc) immunoreactivity copurified with growth cones, Experiments involving ligand-activated receptor autophosphorylation confirmed the concentration of IGF-I but not of insulin receptors in growth cone fractions. These results indicate the enrichment of IGF-I receptors in (presumably axonal) growth cones of the differentiating neuron, Furthermore, the segregation of beta(gc) from AbP2 immunoreactivity suggests that such neurons express an immunochemically distinct variant of the IGF-I receptor beta subunit at the growth cone.