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A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
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LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses
Alessandra Sclip1, Thomas C Südhof1
1Department of Cellular and Molecular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States.
Elife
|January 28, 2020
Summary
LAR-type receptor phosphotyrosine-phosphatases (LAR-RPTPs) do not form synapses but regulate their function. Deleting LAR-RPTPs impairs NMDA receptor responses, revealing their role in controlling synaptic properties.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- LAR-type receptor phosphotyrosine-phosphatases (LAR-RPTPs) are presynaptic adhesion molecules.
- They are believed to mediate synapse formation through trans-synaptic interactions with postsynaptic molecules like SliTrks, SALMs, and TrkC.
Purpose of the Study:
- To investigate the role of LAR-RPTPs in synapse formation and function.
- To determine if LAR-RPTPs are essential for establishing synaptic connectivity.
Main Methods:
- Conditional gene deletion of all three LAR-RPTPs in mice prior to synapse formation.
- Assessment of synaptic connectivity in cultured neurons and in vivo using electrophysiological recordings (AMPA and NMDA receptor-mediated responses).
Main Results:
- Deletion of LAR-RPTPs did not affect overall synaptic connectivity in cultured neurons or in vivo.
- LAR-RPTP deletion significantly impaired NMDA-receptor-mediated responses, indicating a role in regulating synaptic function.
- This impairment occurred via a trans-synaptic mechanism without altering NMDA receptor subunit composition or protein levels.
Conclusions:
- LAR-RPTPs are not essential for the formation of synapses.
- LAR-RPTPs play a crucial role in controlling synapse properties, specifically by regulating postsynaptic NMDA-receptors.
- This regulation is achieved through trans-synaptic mechanisms involving interactions with postsynaptic ligands.
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