Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration

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 (S1...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2016-12, Vol.5
Main Authors: Ko, Hyo Rim, Kwon, Il-Sun, Hwang, Inwoo, Jin, Eun-Ju, Shin, Joo-Ho, Brennan-Minnella, Angela M, Swanson, Raymond, Cho, Sung-Woo, Lee, Kyung-Hoon, Ahn, Jee-Yin
Format: Article
Language:English
Subjects:
AKT
AKT protein
AKT1 protein
Animals
axon growth
axon regeneration
Axonogenesis
Axons
Axons - physiology
Binding sites (Biochemistry)
Brain research
Cell Biology
Central nervous system
Central Nervous System - cytology
Cytoskeletal Proteins - metabolism
Deoxyribonucleic acid
developing neuron
DNA
DNA sequencing
Genetic aspects
growth cone
Growth Cones - physiology
Hippocampus
Id2
Id2 protein
Inhibitor of Differentiation Protein 2 - metabolism
Kinases
Localization
Medicine
Membrane Proteins - metabolism
Methods
Mice
Nervous system
Neural circuitry
Neurons
Nucleotide sequencing
Observations
Phosphorylation
Proteasomes
Protein Processing, Post-Translational
Proteins
Proto-Oncogene Proteins c-akt - metabolism
Radixin
Rats
Regeneration
Reinstatement
Serine
Signal transduction
Statistical analysis
Transcription factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.20799