Ptpσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission

Seung Ko Ji, Pramanikb Gopal, Won Uma Ji, Seon Shimd Ji, Dongmin Lee, Hun Kimf Kee, Chunga Gug-Young, Condomittig Giuseppe, Min Kimf Ho, Hyun Kim, Wit De Joris, Park Kang-Sik, Tabuchi Katsuhiko, Ko Jaewon

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Abstract

Leukocyte common antigen-related receptor protein tyrosine phosphatases-comprising LAR, PTPaδ, and PTPoσ-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 PTPσPTPσ 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 PTPoσ 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. PTPσglypicanLRRTM4 synaptic cell adhesionheparan sulfate.

Original languageEnglish
Pages (from-to)1874-1879
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number6
DOIs
Publication statusPublished - 2015 Feb 10

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Cite this

Ji, S. K., Gopal, P., Ji, W. U., Ji, S. S., Lee, D., Kee, H. K., Gug-Young, C., Giuseppe, C., Ho, M. K., Kim, H., De Joris, W., Kang-Sik, P., Katsuhiko, T., & Jaewon, K. (2015). Ptpσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission. Proceedings of the National Academy of Sciences of the United States of America, 112(6), 1874-1879. https://doi.org/10.1073/pnas.1410138112