ノズミ　モトヒロ   野住　素広    所属   新潟薬科大学  医療技術学部 臨床検査学科    職種   教授
言語種別	英語
発行・発表の年月	2022/09
形態種別	論文 - 研究論文（学術雑誌）
査読	査読あり
標題	JNK1-Dependent Phosphorylation of GAP-43 Serine 142 is a Novel Molecular Marker for Axonal Growth.
執筆形態	その他 - 指定なし
掲載誌名	Neurochemical research
掲載区分	国外
巻・号・頁	47(9),pp.2668-2682
著者・共著者	Masayasu Okada,Yosuke Kawagoe,Toshiyuki Takasugi,Motohiro Nozumi,Yasuyuki Ito,Hayato Fukusumi,Yonehiro Kanemura,Yukihiko Fujii,Michihiro Igarashi
概要	Mammalian axon growth has mechanistic similarities with axon regeneration. The growth cone is an important structure that is involved in both processes, and GAP-43 (growth associated protein-43 kDa) is believed to be the classical molecular marker. Previously, we used growth cone phosphoproteomics to demonstrate that S96 and T172 of GAP-43 in rodents are highly phosphorylated sites that are phosphorylated by c-jun N-terminal protein kinase (JNK). We also revealed that phosphorylated (p)S96 and pT172 antibodies recognize growing axons in the developing brain and regenerating axons in adult peripheral nerves. In rodents, S142 is another putative JNK-dependent phosphorylation site that is modified at a lower frequency than S96 and T172. Here, we characterized this site using a pS142-specific antibody. We confirmed that pS142 was detected by co-expressing mouse GAP-43 and JNK1. pS142 antibody labeled growth cones and growing axons in developing mouse neurons. pS142 was sustained until at least nine weeks after birth in mouse brains. The pS142 antibody could detect regenerating axons following sciatic nerve injury in adult mice. Comparison of amino acid sequences indicated that rodent S142 corresponds to human S151, which is predicted to be a substrate of the MAPK family, which includes JNK. Thus, we confirmed that the pS142 antibody recognized human phospho-GAP-43 using activated JNK1, and also that its immunostaining pattern in neurons differentiated from human induced pluripotent cells was similar to those observed in mice. These results indicate that the S142 residue is phosphorylated by JNK1 and that the pS142 antibody is a new candidate molecular marker for axonal growth in both rodents and human.
DOI	10.1007/s11064-022-03580-6
PMID	35347634