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

ELife
Kyungdeok KimEunjoon Kim

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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Citations

Sep 29, 2020·Frontiers in Cellular Neuroscience·Alfred Kihoon LeeHideto Takahashi
Jan 10, 2021·Nature Reviews. Neuroscience·Andrea M GomezPeter Scheiffele
Aug 10, 2021·Frontiers in Synaptic Neuroscience·Angelina LesnikovaEero Castrén
Oct 1, 2021·Communications Biology·Eunkyung LieEunjoon Kim

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Methods Mentioned

BETA
PCR
genotyping
pull down
GTPase
dissection
transfection

Software Mentioned

Socerer
Clampex
GraphPad Prism
EthoVision XT
DAVID GO
SynGO
DAVID
EthoVision XT12
LABORAS
Clampfit

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