PTP sigma functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission
- Authors
- Ko, Ji Seung; Pramanik, Gopal; Um, Ji Won; Shim, Ji Seon; Lee, Dongmin; Kim, Kee Hun; Chung, Gug-Young; Condomitti, Giuseppe; Kim, Ho Min; Kim, Hyun; de Wit, Joris; Park, Kang-Sik; Tabuchi, Katsuhiko; Ko, Jaewon
- Issue Date
- 10-2월-2015
- Publisher
- NATL ACAD SCIENCES
- Keywords
- PTPs; glypican; LRRTM4; synaptic cell adhesion; heparan sulfate
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.112, no.6, pp.1874 - 1879
- Indexed
- SCIE
SCOPUS
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 112
- Number
- 6
- Start Page
- 1874
- End Page
- 1879
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/94405
- DOI
- 10.1073/pnas.1410138112
- ISSN
- 0027-8424
- Abstract
- Leukocyte common antigen-related receptor protein tyrosine phosphatases-comprising LAR, PTP delta, and PTP sigma-are synaptic adhesion molecules that organize synapse development. Here, we identify glypican 4 (GPC-4) as a ligand for PTP sigma. GPC-4 showed strong (nanomolar) affinity and heparan sulfate (HS)-dependent interaction with the Ig domains of PTP sigma. PTP sigma 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 PTP sigma, 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, PTP sigma KD dramatically decreased both the frequency and amplitude of excitatory synaptic transmission. This effect was reversed by wild-type PTP sigma, but not by a HS-binding-defective PTP sigma mutant. Our results collectively suggest that presynaptic PTP sigma, together with GPC-4, acts in a HS-dependent manner to maintain excitatory synapse development and function.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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