Akt1-Inhibitor of DNA Binding2 is Essential for Growth Cone Formation and Axon Growth and Promotes Central Nervous System Axon Regeneration

Overview

Journal Elife

Specialty Biology

Date 2016 Dec 13

PMID 27938661

Citations 15

Authors

Hyo Rim Ko

Il-Sun Kwon

Inwoo Hwang

Eun-Ju Jin

Joo-Ho Shin

Angela M Brennan-Minnella

Raymond Swanson

Sung-Woo Cho

Kyung-Hoon Lee

Jee-Yin Ahn

Affiliations

Soon will be listed here.

Abstract

Mechanistic studies of axon growth during development are beneficial to the search for neuron-intrinsic regulators of axon regeneration. Here, we discovered that, in the developing neuron from rat, Akt signaling regulates axon growth and growth cone formation through phosphorylation of serine 14 (S14) on Inhibitor of DNA binding 2 (Id2). This enhances Id2 protein stability by means of escape from proteasomal degradation, and steers its localization to the growth cone, where Id2 interacts with radixin that is critical for growth cone formation. Knockdown of or abrogation of Id2 phosphorylation at S14, greatly impairs axon growth and the architecture of growth cone. Intriguingly, reinstatement of Akt/Id2 signaling after injury in mouse hippocampal slices redeemed growth promoting ability, leading to obvious axon regeneration. Our results suggest that Akt/Id2 signaling is a key module for growth cone formation and axon growth, and its augmentation plays a potential role in CNS axonal regeneration.

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