title: Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration.
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 ofId2,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.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyo Rim
authors.initials: HR
authors.lastname: Ko
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Il-Sun
authors.initials: IS
authors.lastname: Kwon
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Inwoo
authors.initials: I
authors.lastname: Hwang
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Jin
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Shin
authors.affiliation: The Department of Neurology, University of California, San Francisco Medical Center, San Francisco, United States.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Brennan-Minnella
authors.affiliation: The Department of Neurology, University of California, San Francisco Medical Center, San Francisco, United States.
authors.forename: Raymond
authors.identifier: 0000-0002-3664-5359
authors.initials: R
authors.lastname: Swanson
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Department of Anatomy, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jee-Yin
authors.identifier: 0000-0003-0002-008X
authors.initials: JY
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D020439:Growth Cones / Q000502:physiology*; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D012038:Regeneration
chemical_list: D003598:Cytoskeletal Proteins; C497451:Id2 protein, rat; D051797:Inhibitor of Differentiation Protein 2; D008565:Membrane Proteins; C071776:radixin; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Id2; axon growth; axon regeneration; cell biology; developing neuron; growth cone; mouse