Long-term Potentiation Reconstituted with an Artificial TARP/PSD-95 Complex

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 Oct 12

PMID 36223737

Authors

Anagh Sinha Ravi

Menglong Zeng

Xudong Chen

Gerardo Sandoval

Javier Diaz-Alonso

Mingjie Zhang

Roger A Nicoll

Affiliations

Soon will be listed here.

Abstract

The critical role of AMPA receptor (AMPAR) trafficking in long-term potentiation (LTP) of excitatory synaptic transmission is now well established, but the underlying molecular mechanism is still uncertain. Recent research suggests that PSD-95 captures AMPARs via an interaction with the AMPAR auxiliary subunits-transmembrane AMPAR regulatory proteins (TARPs). To determine if such interaction is a core minimal component of the AMPAR trafficking and LTP mechanism, we engineered artificial binding partners, which individually were biochemically and functionally dead but which, when expressed together, rescue binding and both basal synaptic transmission and LTP. These findings establish the TARP/PSD-95 complex as an essential interaction underlying AMPAR trafficking and LTP.

Citing Articles

AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.

Choquet D, Opazo P, Zhang H Transl Neurodegener. 2025; 14(1):8.

PMID: 39934896 PMC: 11817889. DOI: 10.1186/s40035-025-00470-z.

The VGCC auxiliary subunit α2δ1 is an extracellular GluA1 interactor and regulates LTP, spatial memory, and seizure susceptibility.

Leana-Sandoval G, Kolli A, Sandoval M, Saavedra E, Li K, Chen L bioRxiv. 2024; .

PMID: 39677598 PMC: 11642997. DOI: 10.1101/2024.12.02.626379.

PSD-95 Protein: A Promising Therapeutic Target in Chronic Pain.

Ma L, Sun D, Wen S, Yuan J, Li J, Tan X Mol Neurobiol. 2024; 62(3):3361-3375.

PMID: 39285025 DOI: 10.1007/s12035-024-04485-x.

Differential Alterations in the Expression of AMPA Receptor and Its Trafficking Proteins in the Hippocampus Are Associated with Recognition Memory Impairment in the Rotenone-Parkinson's Disease Mouse Model: Neuroprotective Role of Bacopa monnieri....

Gupta V, Prasad S Mol Neurobiol. 2024; 62(2):2086-2104.

PMID: 39073529 DOI: 10.1007/s12035-024-04392-1.

Targeting TrkB-PSD-95 coupling to mitigate neurological disorders.

Yang X, Huang Y, Marshall J Neural Regen Res. 2024; 20(3):715-724.

PMID: 38886937 PMC: 11433911. DOI: 10.4103/NRR.NRR-D-23-02000.

References

Ehrlich I, Malinow R . Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J Neurosci. 2004; 24(4):916-27. PMC: 6729816. DOI: 10.1523/JNEUROSCI.4733-03.2004. View

Elias G, Elias L, Apostolides P, Kriegstein A, Nicoll R . Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development. Proc Natl Acad Sci U S A. 2008; 105(52):20953-8. PMC: 2634944. DOI: 10.1073/pnas.0811025106. View

Dakoji S, Tomita S, Karimzadegan S, Nicoll R, Bredt D . Interaction of transmembrane AMPA receptor regulatory proteins with multiple membrane associated guanylate kinases. Neuropharmacology. 2003; 45(6):849-56. DOI: 10.1016/s0028-3908(03)00267-3. View

Hayashi Y, Shi S, Esteban J, Piccini A, Poncer J, Malinow R . Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Science. 2000; 287(5461):2262-7. DOI: 10.1126/science.287.5461.2262. View

Zeng M, Diaz-Alonso J, Ye F, Chen X, Xu J, Ji Z . Phase Separation-Mediated TARP/MAGUK Complex Condensation and AMPA Receptor Synaptic Transmission. Neuron. 2019; 104(3):529-543.e6. PMC: 6842113. DOI: 10.1016/j.neuron.2019.08.001. View

Elias G, Nicoll R . Synaptic trafficking of glutamate receptors by MAGUK scaffolding proteins. Trends Cell Biol. 2007; 17(7):343-52. DOI: 10.1016/j.tcb.2007.07.005. View

Sheng M, Hoogenraad C . The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu Rev Biochem. 2007; 76:823-47. DOI: 10.1146/annurev.biochem.76.060805.160029. View

Fukata Y, Chen X, Chiken S, Hirano Y, Yamagata A, Inahashi H . LGI1-ADAM22-MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention. Proc Natl Acad Sci U S A. 2021; 118(3). PMC: 7826393. DOI: 10.1073/pnas.2022580118. View

Granger A, Shi Y, Lu W, Cerpas M, Nicoll R . LTP requires a reserve pool of glutamate receptors independent of subunit type. Nature. 2012; 493(7433):495-500. PMC: 3998843. DOI: 10.1038/nature11775. View

10.

Chen X, Fukata Y, Fukata M, Nicoll R . MAGUKs are essential, but redundant, in long-term potentiation. Proc Natl Acad Sci U S A. 2021; 118(28). PMC: 8285982. DOI: 10.1073/pnas.2107585118. View

11.

Diaz-Alonso J, Sun Y, Granger A, Levy J, Blankenship S, Nicoll R . Subunit-specific role for the amino-terminal domain of AMPA receptors in synaptic targeting. Proc Natl Acad Sci U S A. 2017; 114(27):7136-7141. PMC: 5502653. DOI: 10.1073/pnas.1707472114. View

12.

Ye F, Liu W, Shang Y, Zhang M . An Exquisitely Specific PDZ/Target Recognition Revealed by the Structure of INAD PDZ3 in Complex with TRP Channel Tail. Structure. 2016; 24(3):383-91. DOI: 10.1016/j.str.2015.12.013. View

13.

Chen X, Vinade L, Leapman R, Petersen J, Nakagawa T, Phillips T . Mass of the postsynaptic density and enumeration of three key molecules. Proc Natl Acad Sci U S A. 2005; 102(32):11551-6. PMC: 1182136. DOI: 10.1073/pnas.0505359102. View

14.

Shi Y, Lu W, Milstein A, Nicoll R . The stoichiometry of AMPA receptors and TARPs varies by neuronal cell type. Neuron. 2009; 62(5):633-40. PMC: 3119531. DOI: 10.1016/j.neuron.2009.05.016. View

15.

Shi S, Hayashi Y, Esteban J, Malinow R . Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell. 2001; 105(3):331-43. DOI: 10.1016/s0092-8674(01)00321-x. View

16.

Groc L, Choquet D . Linking glutamate receptor movements and synapse function. Science. 2020; 368(6496). DOI: 10.1126/science.aay4631. View

17.

Nicoll R . A Brief History of Long-Term Potentiation. Neuron. 2017; 93(2):281-290. DOI: 10.1016/j.neuron.2016.12.015. View

18.

Sumioka A, Yan D, Tomita S . TARP phosphorylation regulates synaptic AMPA receptors through lipid bilayers. Neuron. 2010; 66(5):755-67. PMC: 2887694. DOI: 10.1016/j.neuron.2010.04.035. View

19.

Diaz-Alonso J, Morishita W, Incontro S, Simms J, Holtzman J, Gill M . Long-term potentiation is independent of the C-tail of the GluA1 AMPA receptor subunit. Elife. 2020; 9. PMC: 7500950. DOI: 10.7554/eLife.58042. View

20.

Cheng D, Hoogenraad C, Rush J, Ramm E, Schlager M, Duong D . Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol Cell Proteomics. 2006; 5(6):1158-70. DOI: 10.1074/mcp.D500009-MCP200. View