NME2 associates with PTPσ to transduce signals from chondroitin sulfate proteoglycans

Hajime Hamasaki; Masashi Fujitani; Toshihide Yamashita

doi:10.1016/j.bbrc.2016.02.042

NME2 associates with PTPσ to transduce signals from chondroitin sulfate proteoglycans

Biochem Biophys Res Commun. 2016 Mar 18;471(4):522-7. doi: 10.1016/j.bbrc.2016.02.042. Epub 2016 Feb 16.

Authors

Hajime Hamasaki¹, Masashi Fujitani², Toshihide Yamashita³

Affiliations

¹ 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.
² 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.
³ 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.

PMID: 26896769
DOI: 10.1016/j.bbrc.2016.02.042

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.

Keywords: Axon outgrowth; CSPGs; NME2; PTPσ.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Nucleus / enzymology
Cerebral Cortex / cytology
Chondroitin Sulfate Proteoglycans / metabolism*
Chondroitin Sulfate Proteoglycans / pharmacology
Cytoplasm / enzymology
Gene Knockdown Techniques
HEK293 Cells
Humans
Mass Spectrometry
Mice
NM23 Nucleoside Diphosphate Kinases / genetics
NM23 Nucleoside Diphosphate Kinases / metabolism*
Neurites / drug effects
Neurites / metabolism
Neurites / physiology*
Neurons / enzymology
Neurons / ultrastructure
Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics
Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*

Substances

Chondroitin Sulfate Proteoglycans
NM23 Nucleoside Diphosphate Kinases
Nme2 protein, mouse
Ptprs protein, mouse
Receptor-Like Protein Tyrosine Phosphatases, Class 2