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IGF-1 receptor is essential for the establishment of hippocampal neuronal polarity

Nature Neuroscience volume 9, pages 993–995 (2006)Cite this article

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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Figure 1: Reducing IGF-1R function by incubation with blocking antibody or by siRNA silencing prevents axon formation in rat hippocampal neurons.
Figure 2: Cotransfection of neurons with IGF-1R–targeted siRNA and cDNA encoding fc- Cdc-42 rescues the phenotype.

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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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Authors and Affiliations

  1. Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba y Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Consejo de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina

    Lucas Sosa, Sebastian Dupraz, Lisandro Laurino & Santiago Quiroga

  2. Instituto de Investigaciones Mercedes y Martin Ferreyra (INIMEC-CONICET), Córdoba, Argentina

    Flavia Bollati, Mariano Bisbal & Alfredo Cáceres

  3. Department of Pediatrics, University of Colorado School of Medicine and University of Colorado Cancer Center, Aurora, 80045, Colorado, USA

    Karl H Pfenninger

Authors
  1. Lucas Sosa
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  2. Sebastian Dupraz
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  3. Lisandro Laurino
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  4. Flavia Bollati
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  5. Mariano Bisbal
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  6. Alfredo Cáceres
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  7. Karl H Pfenninger
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  8. Santiago Quiroga
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Corresponding author

Correspondence to Santiago Quiroga.

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The authors declare no competing financial interests.

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)

Supplementary Methods (PDF 130 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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