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

Nerve growth cones isolated from fetal rat brain are highly enriched i n a 97-kDa glycoprotein, termed beta(gc), that comigrates with the bet a subunit of the IGF-I receptor upon two-dimensional PAGE and is disul fide-linked to this receptor's ct subunit. Antibodies prepared to a co nserved 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 imm unoreactivity away from growth cones, whereas most beta(gc) immunoreac tivity copurified with growth cones, Experiments involving ligand-acti vated 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) gro wth cones of the differentiating neuron, Furthermore, the segregation of beta(gc) from AbP2 immunoreactivity suggests that such neurons expr ess an immunochemically distinct variant of the IGF-I receptor beta su bunit at the growth cone.