PI3K activation by IGF-1 is essential for the regulation of membrane expansion at the nerve growth cone

LAURINO, L.; XIAOXIN, X.; DE LA HOUSSAYE, B.; SOSA, L; DUPRAZ, S.; CACERES, A.; PFENNINGER, K.; QUIROGA, S.

JOURNAL OF CELL SCIENCE

The Company of Biologist

Año: 2005 vol. 118 p. 3653 - 3662

0021-9533

Exocytotic incorporation of plasmalemmal precursor vesicles (PPVs) into the cell  surface is necessary for axonal outgrowth and is known to occur mainly at the nerve  growth cone. We have demonstrated recently that plasmalemmal expansion is regulated  at the growth cone by IGF-1, but not by BDNF, in a manner that is quasi independent of  the neuron’s perikaryon. In order to begin elucidating the signaling pathway by which  exocytosis of the plasmalemmal precursor is regulated, we studied activation of the  IRS/PI3k/Akt pathway in isolated growth cones and hippocampal neurons in culture  stimulated with IGF-1 or BDNF. Our results show that IGF-1, but not BDNF,  significantly and rapidly stimulates IRS/PI3k/Akt and membrane expansion. Inhibition  of PI3k with Wortmannin or LY294002 blocked IGF-1-stimulated plasmalemmal  expansion at the growth cones of cultured neurons. Finally, our results show that, upon  stimulation with IGF-1, most active PI3k becomes associated with distal microtubules  in the proximal or central domain of the growth cone. Taken together, our results  suggest a critical role for IGF-1 and the IRS/PI3k/Akt pathway in the process of  membrane assembly at the axonal growth cone.