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 language | English |
|---|---|
| Pages (from-to) | 190-203 |
| Number of pages | 14 |
| Journal | Food Science and Human Wellness |
| Volume | 4 |
| DOIs | |
| Publication status | Published - 2018 Jun 29 |
| Externally published | Yes |
Fingerprint
Keywords
- Bioinformatics
- Developmental Neuroscience
- Neuroscience
- Proteomics
ASJC Scopus subject areas
- Food Science
- General
Cite this
Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a Marker of Axon Growth and Regeneration. / Kawasaki, Asami; Okada, Masayasu; Tamada, Atsushi; Okuda, Shujiro; Nozumi, Motohiro; Ito, Yasuyuki; Kobayashi, Daiki; Yamasaki, Tokiwa; Yokoyama, Ryo; Shibata, Takeshi; Nishina, Hiroshi; Yoshida, Yutaka; Fujii, Yukihiko; Takeuchi, Kosei; Igarashi, Michihiro.
In: Food Science and Human Wellness, Vol. 4, 29.06.2018, p. 190-203.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a Marker of Axon Growth and Regeneration
AU - Kawasaki, Asami
AU - Okada, Masayasu
AU - Tamada, Atsushi
AU - Okuda, Shujiro
AU - Nozumi, Motohiro
AU - Ito, Yasuyuki
AU - Kobayashi, Daiki
AU - Yamasaki, Tokiwa
AU - Yokoyama, Ryo
AU - Shibata, Takeshi
AU - Nishina, Hiroshi
AU - Yoshida, Yutaka
AU - Fujii, Yukihiko
AU - Takeuchi, Kosei
AU - Igarashi, Michihiro
PY - 2018/6/29
Y1 - 2018/6/29
N2 - 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.
AB - 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.
KW - Bioinformatics
KW - Developmental Neuroscience
KW - Neuroscience
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=85065655786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065655786&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2018.05.019
DO - 10.1016/j.isci.2018.05.019
M3 - Article
AN - SCOPUS:85065655786
VL - 4
SP - 190
EP - 203
JO - Food Science and Human Wellness
JF - Food Science and Human Wellness
SN - 2213-4530
ER -