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Volume 17, Number 4, Issue of February 15, 1997 pp. 1447-1459
Copyright ©1997 Society for Neuroscience

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

Received Aug. 27, 1996; revised Nov. 12, 1996; accepted Dec. 3, 1996.

Faustino Mascotti¹, Alfredo Cáceres¹, Karl H. Pfenninger², and Santiago Quiroga³

¹ Instituto Investigación Médica Mercedes y Martín Ferreya, Córdoba, Argentina, ² Department of Cellular and Structural Biology, University of Colorado School of Medicine, Denver, Colorado, and ³ Departamento Química Biológica, Facultad Ciencias Químicas, Universidad Nacional de Córdoba/Consejo Nacional de Investigaciónes Científicas y Técnicas, Córdoba, Argentina

_gc is a -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 _gc in developing neurons and differentiating PC12 cells. In the developing cerebral cortex and, at least at early stages, in cultured primary neurons, _gc expression was found to be correlated with neurite outgrowth. In PC12 cells _gc expression was nerve growth factor (NGF)-dependent and also paralleled neurite outgrowth. In contrast, -subunits of the insulin receptor and/or of other IGF-1 receptors ("_P5"; detected with antibody AbP5) were downregulated as _gc expression increased. Immunofluorescence studies confirmed the enrichment of _gc at growth cones and demonstrated morphologically its spatial separation from _P5, which is confined to the perikaryon. At the growth cone, _gc colocalizes and associates in a proximal region with microtubules, but it seems independent of the more peripheral microfilaments. Some _gc immunoreactivity is detected in the perinuclear region of PC12 cells, most likely the Golgi complex and its vicinity. _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) _gc expression is correlated closely with neurite outgrowth, that (2) it is regulated in PC12 cells by a neurotrophin, NGF, and that (3) _gc is concentrated in the proximal growth cone region raise new questions regarding a possible role of IGF-1 receptors containing _gc in the regulation of neurite growth.

Key words: IGF-1 receptor; -subunits; _gc; growth cones; neurons; neurite outgrowth; neurotrophins; PC12 cells; development; tissue culture

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