citations

                    NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC
                

Authors:

Zhou FQ, Zhou J, Dedhar S, Wu YH and Snider WD

In:

Source: Neuron
Publication Date: (2004)
Issue: 42(6): 897-912

Research Area:

Neurobiology

Cells used in publication:

Dorsal root ganglion (DRG), mouse: Species: mouse; Tissue Origin: brain

Platform:

Nucleofector® I/II/2b

Experiment

DRG Neurons overexpressing the GSK-3beta; inhibiting protein Frat-1 showed a quantifiable inhibition effect on GSK-3beta; and axon growth. Nucleofection with wild-type Rac, a small GTPase with an inducing effect on actin polymerization, enabled the authors to conduct APC localisation studies in enlarged growth cones. Expression of several GFP-tagged mutant forms of APC and of an APC-binding protein binding partner revealed detailed functions of protein domains for spatial localization and axon growth.

Abstract

Little is known about how nerve growth factor (NGF) signaling controls the regulated assembly of microtubules that underlies axon growth. Here we demonstrate that a tightly regulated and localized activation of phosphatidylinositol 3-kinase (PI3K) at the growth cone is essential for rapid axon growth induced by NGF. This spatially activated PI3K signaling is conveyed downstream through a localized inactivation of glycogen synthase kinase 3beta (GSK-3beta). These two spatially coupled kinases control axon growth via regulation of a microtubule plus end binding protein, adenomatous polyposis coli (APC). Our results demonstrate that NGF signals are transduced to the axon cytoskeleton via activation of a conserved cell polarity signaling pathway.

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