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Journal of Neuroscience, Vol 14, 6412-6422, Copyright © 1994 by Society for Neuroscience
Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system
F Folli, L Bonfanti, E Renard, CR Kahn and A Merighi
Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Insulin receptor substrate 1 (IRS-1) is the primary cytosolic substrate of
the insulin and insulin-like growth factor-I (IGF-I) receptors. Following
tyrosine phosphorylation IRS-1 binds to and activates specific proteins
containing SH2 domains. Using biochemical and immunocytochemical
techniques, we have mapped the distribution of IRS-1 in the CNS of the
adult rat and compared it with that of insulin and IGF-I receptors and
phosphatidylinositol 3-kinase (PI-3 kinase), a signaling molecule
functionally related to IRS-1. Immunoprecipitation and Western blotting
experiments demonstrate the presence of substantial amounts of IRS-1,
insulin receptor, and PI-3 kinase in the brain. IRS-1 immunoreactivity is
widely distributed in neurons from several areas of the brain and spinal
cord. The cerebral cortex, the hippocampus, many hypothalamic and thalamic
nuclei, the basal ganglia, the cerebellar cortex, the brainstem nuclei, and
the lamina X of the spinal cord are particularly rich of immunopositive
nerve cells. In these areas most of the neurons immunoreactive for IRS-1
are also stained by either anti-insulin receptor or anti-IGF-I receptor
antibodies as well as PI-3 kinase antiserum. IRS-1 immunostaining was very
weak or totally absent in neurons of the olfactory bulb, the supraoptic and
paraventricular nuclei, the mesencephalic trigeminal nucleus, and the
granule cell layer of the cerebellum, despite the fact that these areas
were immunolabeled with antibodies against insulin or IGF-I receptors
and/or PI-3 kinase. These results show that neurons in the adult rat CNS
are endowed with some of the components of the early signaling pathway for
growth factors of the insulin/IGF-I family, although IRS-1 has a
distribution distinct from that of the two receptors.
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