TY - JOUR TI - Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration AU - Ko, Hyo Rim AU - Kwon, Il-Sun AU - Hwang, Inwoo AU - Jin, Eun-Ju AU - Shin, Joo-Ho AU - Brennan-Minnella, Angela M AU - Swanson, Raymond AU - Cho, Sung-Woo AU - Lee, Kyung-Hoon AU - Ahn, Jee-Yin A2 - Kim, Eunjoon VL - 5 PY - 2016 DA - 2016/12/12 SP - e20799 C1 - eLife 2016;5:e20799 DO - 10.7554/eLife.20799 UR - https://doi.org/10.7554/eLife.20799 AB - 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 Id2, 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. KW - axon growth KW - AKT KW - Id2 KW - growth cone KW - developing neuron KW - axon regeneration JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -