Presynaptic PTPσ regulates postsynaptic NMDA receptor function through direct adhesion-independent mechanisms
- Korea Advanced Institute of Science and Technology, Republic of Korea
- Institute for Basic Science, Republic of Korea
- Kyungpook National University, Republic of Korea
- Korea University, Republic of Korea
- Institute for Basic Science, Korea Advanced Institute of Science and Technology, Republic of Korea
Abstract
Synaptic adhesion molecules regulate synapse development and function. However, whether and how presynaptic adhesion molecules regulate postsynaptic NMDAR function remains largely unclear. Presynaptic LAR family receptor tyrosine phosphatases (LAR-RPTPs) regulate synapse development through mechanisms that include trans-synaptic adhesion; however, whether they regulate postsynaptic receptor functions remains unknown. Here we report that presynaptic PTPσ, a LAR-RPTP, enhances postsynaptic NMDA receptor (NMDAR) currents and NMDAR-dependent synaptic plasticity in the hippocampus. This regulation does not involve trans-synaptic adhesions of PTPσ, suggesting that the cytoplasmic domains of PTPσ, known to have tyrosine phosphatase activity and mediate protein-protein interactions, are important. In line with this, phosphotyrosine levels of presynaptic proteins, including neurexin-1, are strongly increased in PTPσ-mutant mice. Behaviorally, PTPσ-dependent NMDAR regulation is important for social and reward-related novelty recognition. These results suggest that presynaptic PTPσ regulates postsynaptic NMDAR function through trans-synaptic and direct adhesion-independent mechanisms and novelty recognition in social and reward contexts.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Institute for Basic Science (IBS-R002-D1)
- Eunjoon Kim
The National Research Foundation of Korea (MSIT,NRF-2017R1A5A2015391)
- Yong Chul Bae
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mice were housed and bred at the mouse facility of Korea Advanced Institute of Science and Technology (KAIST) and maintained according to the Animal Research Requirements of KAIST. All procedures were approved by the Committee of Animal Research at KAIST (KA2016-33)
Copyright
© 2020, Kim et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Presynaptic PTPσ regulates postsynaptic NMDA receptor function through direct adhesion-independent mechanisms
eLife 9:e54224.
https://doi.org/10.7554/eLife.54224
