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

被引:93
|
作者
Laurino, L
Wang, XXX
de la Houssaye, BA
Sosa, L
Dupraz, S
Cáceres, A
Pfenninger, KH
Quiroga, S [1 ]
机构
[1] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Quim Biol, RA-5000 Cordoba, Argentina
[2] Consejo Nacl Invest Cient & Tecn, CIQUIBIC, RA-5000 Cordoba, Argentina
[3] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA
[4] Univ Colorado, Sch Med, Dept Cell & Dev Biol, Aurora, CO 80045 USA
[5] Consejo Nacl Invest Cient & Tecn, INIMEC, Inst Invest Mercedes & Martin Ferreyra, RA-5016 Cordoba, Argentina
关键词
IGF-1; PI3K/Akt; nerve growth cone; axonal outgrowth; membrane expansion;
D O I
10.1242/jcs.02490
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. 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.
引用
收藏
页码:3653 / 3662
页数:10
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