Abstract

β_gc is 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 β_gcin developing neurons and differentiating PC12 cells. In the developing cerebral cortex and, at least at early stages, in cultured primary neurons, β_gc expression was found to be correlated with neurite outgrowth. In PC12 cells β_gc expression 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 (“β_P5”; detected with antibody AbP5) were downregulated as β_gc expression increased. Immunofluorescence studies confirmed the enrichment of β_gc at growth cones and demonstrated morphologically its spatial separation from β_P5, which is confined to the perikaryon. At the growth cone, β_gc colocalizes and associates in a proximal region with microtubules, but it seems independent of the more peripheral microfilaments. Some β_gc immunoreactivity is detected in the perinuclear region of PC12 cells, most likely the Golgi complex and its vicinity. β_gc seems 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) β_gcexpression is correlated closely with neurite outgrowth, that (2) it is regulated in PC12 cells by a neurotrophin, NGF, and that (3) β_gc is concentrated in the proximal growth cone region raise new questions regarding a possible role of IGF-1 receptors containing β_gc in the regulation of neurite growth.