Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a Marker of Axon Growth and Regeneration

Asami Kawasaki, Masayasu Okada, Atsushi Tamada, Shujiro Okuda, Motohiro Nozumi, Yasuyuki Ito, Daiki Kobayashi, Tokiwa Yamasaki, Ryo Yokoyama, Takeshi Shibata, Hiroshi Nishina, Yutaka Yoshida, Yukihiko Fujii, Kosei Takeuchi, Michihiro Igarashi

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Abstract

Neuronal growth cones are essential for nerve growth and regeneration, as well as for the formation and rearrangement of the neural network. To elucidate phosphorylation-dependent signaling pathways and establish useful molecular markers for axon growth and regeneration, we performed a phosphoproteomics study of mammalian growth cones, which identified >30,000 phosphopeptides of ∼1,200 proteins. The phosphorylation sites were highly proline directed and primarily MAPK dependent, owing to the activation of JNK, suggesting that proteins that undergo proline-directed phosphorylation mediate nerve growth in the mammalian brain. Bioinformatics analysis revealed that phosphoproteins were enriched in microtubules and the cortical cytoskeleton. The most frequently phosphorylated site was S96 of GAP-43 (growth-associated protein 43-kDa), a vertebrate-specific protein involved in axon growth. This previously uncharacterized phosphorylation site was JNK dependent. S96 phosphorylation was specifically detected in growing and regenerating axons as the most frequent target of JNK signaling; thus it represents a promising new molecular marker for mammalian axonal growth and regeneration.

Original languageEnglish
Pages (from-to)190-203
Number of pages14
JournalFood Science and Human Wellness
Volume4
DOIs
Publication statusPublished - 2018 Jun 29
Externally publishedYes

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Keywords

  • Bioinformatics
  • Developmental Neuroscience
  • Neuroscience
  • Proteomics

ASJC Scopus subject areas

  • Food Science
  • General

Cite this

Kawasaki, A., Okada, M., Tamada, A., Okuda, S., Nozumi, M., Ito, Y., Kobayashi, D., Yamasaki, T., Yokoyama, R., Shibata, T., Nishina, H., Yoshida, Y., Fujii, Y., Takeuchi, K., & Igarashi, M. (2018). Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a Marker of Axon Growth and Regeneration. Food Science and Human Wellness, 4, 190-203. https://doi.org/10.1016/j.isci.2018.05.019