Abstract
How a neuron becomes polarized remains largely unknown. Results obtained with a function-blocking antibody and an siRNA targeting the insulin-like growth factor-1 (IGF-1) receptor suggest that an essential step in the establishment of hippocampal neuronal polarity and the initiation of axonal outgrowth is the activation of the phosphatidylinositol 3-kinase (PI3k)-Cdc42 pathway by the IGF-1 receptor, but not by the TrkA or TrkB receptors.
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Acknowledgements
This work was supported by grants from Consejo de Investigaciones Científicas y Técnicas (CONICET), Agencia Córdoba Ciencia, Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SECYT-U.N.C.) and Ministerio de Salud, República Argentina (to S.Q.); by the US National Institutes of Health (grant R01 NS41029 to K.H.P.); by a Fogarty International Research Collaboration Award (1R03 TW05763 to K.H.P. and S.Q.); by the Agencia Nacional de Promoción Científica y Tecnológica, Argentina (A.C., S.Q. and G.P.); and by the International Research Scholar Program of the Howard Hughes Medical Institute (HHMI 75197-553201 to A.C.).
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Supplementary information
Supplementary Fig. 1
Specificity of the anti-active IGF-1R antibody. (PDF 281 kb)
Supplementary Fig. 2
Tau did not distribute to a single neurite in αIR3 treated neurons. (PDF 296 kb)
Supplementary Fig. 3
Transfection with an IGF-1R targeted siRNA silenced the expression of βgc-containing IGF-1R to non-detectable levels and inhibited hippocampal neuron polarization. (PDF 230 kb)
Supplementary Fig. 4
siRNA-treated neurons showed no significant differences in viability, whereas significant differences were evident in neuronal polarization. (PDF 351 kb)
Supplementary Fig. 5
siRNA treated neurons expressed near-normal levels of activatable BDNF receptor but were unable to form axons. (PDF 327 kb)
Supplementary Fig. 6
Neurons expressed insulin receptor (not affected by IGF-1R-targeted siRNA). (PDF 278 kb)
Supplementary Fig. 7
Co-transfection with a dominant-negative form of cdc-42 did not produce any noticeable effects in the IGF-1R-suppressed neurons. (PDF 235 kb)
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Sosa, L., Dupraz, S., Laurino, L. et al. IGF-1 receptor is essential for the establishment of hippocampal neuronal polarity. Nat Neurosci 9, 993–995 (2006). https://doi.org/10.1038/nn1742
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DOI: https://doi.org/10.1038/nn1742
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