Expression and Distribution of IGF-1 Receptors Containing a β-Subunit Variant (βgc) in Developing Neurons

βgcis a β-subunit variant of the insulin-like growth factor-1 (IGF-1) receptor highly enriched in growth cone membranes prepared by subcellular fractionation of fetal rat brain (Quiroga et al., 1995). The present study is focused on the expression and on the cellular and subcellular distribution of βgcin developing neurons and differentiating PC12 cells. In the developing cerebral cortex and, at least at early stages, in cultured primary neurons, βgcexpression was found to be correlated with neurite outgrowth. In PC12 cells βgcexpression was nerve growth factor (NGF)-dependent and also paralleled neurite outgrowth. In contrast, β-subunits of the insulin receptor and/or of other IGF-1 receptors (“βP5”; detected with antibody AbP5) were downregulated as βgcexpression increased. Immunofluorescence studies confirmed the enrichment of βgcat growth cones and demonstrated morphologically its spatial separation from βP5, which is confined to the perikaryon. At the growth cone, βgccolocalizes and associates in a proximal region with microtubules, but it seems independent of the more peripheral microfilaments. Some βgcimmunoreactivity is detected in the perinuclear region of PC12 cells, most likely the Golgi complex and its vicinity. βgcseems to emerge from the periphery of this structure in an apparently vesicular compartment distinct from that carrying synaptophysin to the growth cones. The facts that (1) βgcexpression is correlated closely with neurite outgrowth, that (2) it is regulated in PC12 cells by a neurotrophin, NGF, and that (3) βgcis concentrated in the proximal growth cone region raise new questions regarding a possible role of IGF-1 receptors containing βgcin the regulation of neurite growth.