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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797105 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2022.111483 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Large donor CRISPR for whole-CDS replacement of cell adhesion molecule LRRTM2.
J Neurosci
January 2025
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA
The cell adhesion molecule Leucine-Rich Repeat Transmembrane neuronal protein 2 (LRRTM2) is crucial for synapse development and function. However, our understanding of its endogenous trafficking has been limited due to difficulties in manipulating its coding sequence (CDS) using standard genome editing techniques. Instead, we replaced the entire LRRTM2 CDS by adapting a two-guide CRISPR knock-in method, enabling complete control of LRRTM2.
View Article and Find Full Text PDFAmyloid-β-driven synaptic deficits are mediated by synaptic removal of GluA3-containing AMPA-receptors.
J Neurosci
January 2025
Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA, Amsterdam, The Netherlands.
The detrimental effects of oligomeric amyloid-β (Aβ) on synapses are considered the leading cause for cognitive deficits in Alzheimer's disease. However, through which mechanism Aβ oligomers impair synaptic structure and function remains unknown. Here, we used electrophysiology and AMPA-receptor (AMPAR) imaging on mice and rat neurons to demonstrate that GluA3 expression in neurons lacking GluA3 is sufficient to re-sensitize their synapses to the damaging effects of Aβ, indicating that GluA3-containing AMPARs at synapses are necessary and sufficient for Aβ to induce synaptic deficits.
View Article and Find Full Text PDFLoss of SynDIG4/PRRT1 alters distribution of AMPA receptors in Rab4- and Rab11-positive endosomes and impairs basal AMPA receptor recycling.
bioRxiv
December 2024
Department of Pharmacology, School of Medicine, University of California, Davis, Davis, CA, 95616, USA.
The transmembrane protein Synapse Differentiation Induced Gene 4 (SynDIG4) functions as an auxiliary factor of AMPA receptors (AMPARs) and plays a critical role in excitatory synapse plasticity as well as hippocampal-dependent learning and memory. Mice lacking SynDIG4 have reduced surface expression of GluA1 and GluA2 and are impaired in single tetanus-induced long-term potentiation and NMDA receptor (NMDAR)-dependent long-term depression. These findings suggest that SynDIG4 may play an important role in regulating AMPAR distribution through intracellular trafficking mechanisms; however, the precise roles by which SynDIG4 governs AMPAR distribution remain unclear.
View Article and Find Full Text PDFEdonerpic maleate prevents epileptic seizure during recovery from brain damage by balancing excitatory and inhibitory inputs.
Front Neural Circuits
December 2024
Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Functional recovery from brain damage, such as stroke, is a plastic process in the brain. The excitatory glutamate -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) plays a crucial role in neuronal functions, and the synaptic trafficking of AMPAR is a fundamental mechanism underlying synaptic plasticity. We recently identified a collapsin response mediator protein 2 (CRMP2)-binding compound, edonerpic maleate, which augments rehabilitative training-dependent functional recovery from brain damage by facilitating experience-driven synaptic delivery of AMPARs.
View Article and Find Full Text PDFEpac2-mediated synaptic insertion of Ca-permeable AMPARs in the nucleus accumbens contributes to incubation of cocaine craving.
Neuropsychopharmacology
December 2024
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
The accumulation of GluA2-lacking Ca-permeable AMPARs (CP-AMPARs) in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) is required for the expression of incubation of cocaine craving. The exchange protein directly activated by cAMP (Epac) is an intracellular effector of cAMP and a guanine nucleotide exchange factor for the small GTPase Rap1. Epac2 has been implicated in the trafficking of AMPA receptors at central synapses.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!