Presynaptic PTPσ 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 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.

journal_name

Elife

journal_title

eLife

authors

Kim K,Shin W,Kang M,Lee S,Kim D,Kang R,Jung Y,Cho Y,Yang E,Kim H,Bae YC,Kim E

doi

10.7554/eLife.54224

subject

Has Abstract

pub_date

2020-03-06 00:00:00

issn

2050-084X

pii

54224

journal_volume

9

pub_type

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