title: NME2 associates with PTPσ to transduce signals from chondroitin sulfate proteoglycans.
abstract: Chondroitin sulfate proteoglycans (CSPGs) are a major component of glial scars, inhibiting axonal growth in the central nervous system. Protein tyrosine phosphatase, receptor type S (PTPσ) has been identified as a receptor for CSPGs, whereas its downstream signaling pathway remains to be fully understood. Here, we report that nucleoside diphosphate kinase 2 (NME2) interacts with PTPσ. We screened proteins associated with PTPσ by mass spectrometry, and obtained NME2. Immunoprecipitation analysis revealed that NME2 associated with the PTPσ intracellular domain in HEK-293T cells. NME2 was expressed in the cytoplasm and nucleus of cortical neurons, and knockdown of NME2 in the cortical neurons completely rescued neurite outgrowth inhibition induced by CSPGs. These results demonstrate that NME2 associates with PTPσ to elicit neurite outgrowth inhibition in response to CSPGs.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; JST, CREST, 5, Sanbancho, Chiyoda-ku, Tokyo, 102-0075, Japan; Faculty of Medicine, MD Scientist Training Program, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0872, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Hamasaki
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; JST, CREST, 5, Sanbancho, Chiyoda-ku, Tokyo, 102-0075, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0872, Japan; Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. Electronic address: fujitani@hyo-med.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujitani
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; JST, CREST, 5, Sanbancho, Chiyoda-ku, Tokyo, 102-0075, Japan. Electronic address: yamashita@molneu.med.osaka-u.ac.jp.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D002540:Cerebral Cortex / Q000166:cytology; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism* / Q000494:pharmacology; D003593:Cytoplasm / Q000201:enzymology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000648:ultrastructure; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D054778:NM23 Nucleoside Diphosphate Kinases; C517941:Nme2 protein, mouse; C516885:Ptprs protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: Axon outgrowth; CSPGs; NME2; PTPσ