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Presynaptic PTP? regulates postsynaptic NMDA receptor function through direct adhesion-independent mechanisms.


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 PTP?, 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 PTP?, suggesting that the cytoplasmic domains of PTP?, 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 PTP?-mutant mice. Behaviorally, PTP?-dependent NMDAR regulation is important for social and reward-related novelty recognition. These results suggest that presynaptic PTP? regulates postsynaptic NMDAR function through trans-synaptic and direct adhesion-independent mechanisms and novelty recognition in social and reward contexts.

SUBMITTER: Kim K 

PROVIDER: S-EPMC7069723 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Presynaptic PTPσ regulates postsynaptic NMDA receptor function through direct adhesion-independent mechanisms.

Kim Kyungdeok K   Shin Wangyong W   Kang Muwon M   Lee Suho S   Kim Doyoun D   Kang Ryeonghwa R   Jung Yewon Y   Cho Yisul Y   Yang Esther E   Kim Hyun H   Bae Yong Chul YC   Kim Eunjoon E  

eLife 20200306


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 re  ...[more]

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