Activation of IGF-1 receptors is essential for the establishment of neuronal polarity.

L. SOSA, S. DUPRAZ, L. LAURINO, A. CÁCERES Y S. QUIROGA

Pinamar, Buenos Aires, Argentina

Congreso; X Congress of the Panamerican Association for Biochemistry and Molecular Biology (PABMB), XLI Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology (SAIB), XX Annual Meeting of the Argentine Society for Neurochemistry (SAN).; 2005

PABMB, SAIB y SAN

ACTIVATION OF FETAL INSULIN-LIKE GROWTH FACTOR-1 RECEPTORS BY IGF-1 IS ESSENTIAL FOR THE ESTABLISHMENT OF NEURONAL POLARITY. Sosa, Lucas1, Cáceres, Alfredo2 y Quiroga, Santiago1. 1. Departamento de Química Biológica. CIQUIBIC-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina 2. INIMEC, CONICET, Córdoba, Argentina. How a neuron becomes polarized remains an outstanding question. Recent studies suggest that in cultured hippocampal neurons selection of the future axon requires activation of phosphatidylinositol 3-kinase (PI3k) by growth factor receptor tyrosine kinases. Consistent with this, accumulation of active PI3k and its phospholipid product PIP3 at the growth cone of a minor neurite is crucial for the outgrowth of the future axon and the polarized distribution of mPar3 and mPar6, two proteins required for axon specification. We now provide evidence about the identity of the growth factor-tyrosine kinase receptor system involved in PI3k activation at the growth cone of the future axon. Our results indicate that activation of fetal IGF-1 receptor (containing the subunit bgc) by IGF-1 is essential for axon specification. Suppression of bgc-IGF-1 receptors by siRNA treatment prevents axon formation and the polarized distribution of PI3k-mPar3-mPar6. We also demonstrate that co-transfection of the suppressed cells with a fast-cycling cdc-42 cDNA (a downstream effector of the PI3k pathway involved in neuron polarization) recovers the phenotype inducing outgrowth of a single or several axons. Taken together, our results show that the activation of PI3k pathway by IGF-1 (and not other growth factors as BDNF) is essential for axonal outgrowth and the establishment of neuronal polarity.