Expression and distribution of IGF-1 receptors containing a beta-subunit variant (betagc) in developing neurons

Betagc is a beta-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 (). The present study is focused on the expression and on the cellular and subcellular distribution of betagc in developing neurons and differentiating PC12 cells. In the developing cerebral cortex and, at least at early stages, in cultured primary neurons, betagc expression was found to be correlated with neurite outgrowth. In PC12 cells betagc expression was nerve growth factor (NGF)-dependent and also paralleled neurite outgrowth. In contrast, beta-subunits of the insulin receptor and/or of other IGF-1 receptors ("betaP5"; detected with antibody AbP5) were downregulated as betagc expression increased. Immunofluorescence studies confirmed the enrichment of betagc at growth cones and demonstrated morphologically its spatial separation from betaP5, which is confined to the perikaryon. At the growth cone, betagc colocalizes and associates in a proximal region with microtubules, but it seems independent of the more peripheral microfilaments. Some betagc immunoreactivity is detected in the perinuclear region of PC12 cells, most likely the Golgi complex and its vicinity. betagc 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) betagc expression is correlated closely with neurite outgrowth, that (2) it is regulated in PC12 cells by a neurotrophin, NGF, and that (3) betagc is concentrated in the proximal growth cone region raise new questions regarding a possible role of IGF-1 receptors containing betagc in the regulation of neurite growth.