| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Shim, Ji Seon Lee, Dongmin Kim, Hyun Park, Kang-sik Tabuchi, Katsuhiko Pramanik, Gopal Ko, Ji Seung Ko, Jaewon Chung, Gug-young Condomitti, Giuseppe Kim, Ho Min Kim, Kee Hun De Wit, Joris Um, Ji Won |
| Description |
Author Affiliation: Ko JS ( Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea); Pramanik G ( Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan); Um JW ( Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea); Shim JS ( Department of Physiology, Kyung Hee University School of Medicine, Seoul 130-701, Korea); Lee D ( Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul 136-705, Korea); Kim KH ( Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea); Chung GY ( Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea); Condomitti G ( VIB Center for the Biology of Disease, 3000 Leuven, Belgium); Kim HM ( Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea); Kim H ( Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul 136-705, Korea); de Wit J ( VIB Center for the Biology of Disease, 3000 Leuven, Belgium); Park KS ( Department of Physiology, Kyung Hee University School of Medicine, Seoul 130-701, Korea); Tabuchi K ( Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan); Ko J ( Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea); |
| Abstract |
Leukocyte common antigen-related receptor protein tyrosine phosphatases--comprising LAR, PTPδ, and PTPσ--are synaptic adhesion molecules that organize synapse development. Here, we identify glypican 4 (GPC-4) as a ligand for PTPσ. GPC-4 showed strong (nanomolar) affinity and heparan sulfate (HS)-dependent interaction with the Ig domains of PTPσ. PTPσ bound only to proteolytically cleaved GPC-4 and formed additional complex with leucine-rich repeat transmembrane protein 4 (LRRTM4) in rat brains. Moreover, single knockdown (KD) of PTPσ, but not LAR, in cultured neurons significantly reduced the synaptogenic activity of LRRTM4, a postsynaptic ligand of GPC-4, in heterologous synapse-formation assays. Finally, PTPσ KD dramatically decreased both the frequency and amplitude of excitatory synaptic transmission. This effect was reversed by wild-type PTPσ, but not by a HS-binding-defective PTPσ mutant. Our results collectively suggest that presynaptic PTPσ, together with GPC-4, acts in a HS-dependent manner to maintain excitatory synapse development and function. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
6 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-02-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Brain Metabolism Glypicans Multiprotein Complexes Proteins Receptor-Like Protein Tyrosine Phosphatases, Class 2 Synaptic Transmission Physiology Analysis Of Variance Animals Blotting, Western Chromatography, Affinity Chromatography, High Pressure Liquid Gene Knockdown Techniques Genetic Vectors Genetics Heparitin Sulfate Immunohistochemistry Immunoprecipitation In Situ Hybridization Mass Spectrometry Oligonucleotides Presynaptic Terminals Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
