期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 6, 页码 1874-1879出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1410138112
关键词
PTPs; glypican; LRRTM4; synaptic cell adhesion; heparan sulfate
资金
- Korea Healthcare Technology R&D Project through the Ministry for Health and Welfare Affairs, Republic of Korea [A120590, A120723]
- National Research Foundation of Korea (NRF) - Ministry of Science and Future Planning [2014051826, 2012R1A1A1010456, 2014047939]
- Yonsei University Future-Leading Research Initiative
- NRF - Ministry of Education, Science and Technology [2013R1A6A3A04061338, NRF-2012R1A1A2009219, 2008-0061888]
- NRF Grant NRF-JST Precursory Research for Embryonic Science and Technology
- European Research Council (ERC) Starting Grant [311083]
- Brain Korea 21 (BK21) PLUS program
- BK21 PLUS program
- National Research Foundation of Korea [2013R1A6A3A04061338, 2012R1A1A1010456] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- European Research Council (ERC) [311083] Funding Source: European Research Council (ERC)
- Grants-in-Aid for Scientific Research [25282242] Funding Source: KAKEN
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据