scholarly journals The tetraspanin TSPAN5 regulates AMPARs exocytosis by interacting with the AP-4 complex

2022 ◽  
Author(s):  
Edoardo Moretto ◽  
Anna Longatti ◽  
Federico Miozzo ◽  
Caroline Bonnet ◽  
Francoise Coussen ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Intracellular Trafficking ◽  
Hippocampal Neurons ◽  
Adaptor Proteins ◽  
Deficiency Syndrome ◽  
Receptor Trafficking ◽  
Excitatory Synapses ◽  
Recycling Endosomes ◽  
Intracellular Pool ◽  
Delivery Route

Intracellular trafficking of AMPA receptors is a tightly regulated process which involves several adaptor proteins, and is crucial for the activity of excitatory synapses in both basal conditions and during synaptic plasticity. We found that, in rat hippocampal neurons, an intracellular pool of the tetraspanin TSPAN5 specifically promotes exocytosis of newly synthesised GluA2-containing AMPA receptors without affecting their internalisation. TSPAN5 mediates this function by interacting with AP-4 and Stargazin and possibly using recycling endosomes as a delivery route. This work highlights TSPAN5 as a new adaptor regulating AMPA receptor trafficking. In addition, it provides a possible mechanism for the intellectual disability symptoms that occur in AP-4 deficiency syndrome.

scholarly journals Ligand-independent activity of the ghrelin receptor modulates AMPA receptor trafficking and supports memory formation

2021 ◽  
Vol 14 (670) ◽  
pp. eabb1953
Author(s):  
Luís F. Ribeiro ◽  
Tatiana Catarino ◽  
Mário Carvalho ◽  
Luísa Cortes ◽  
Sandra D. Santos ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Receptor Trafficking ◽  
Excitatory Synapses ◽  
Ghrelin Receptor ◽  
Term Potentiation ◽  
Ghrelin Receptors ◽  
Ampa Receptor Trafficking

The biological signals of hunger, satiety, and memory are interconnected. The role of the hormone ghrelin in regulating feeding and memory makes ghrelin receptors attractive targets for associated disorders. We investigated the effects of the high ligand-independent activity of the ghrelin receptor GHS-R1a on the physiology of excitatory synapses in the hippocampus. Blocking this activity produced a decrease in the synaptic content of AMPA receptors in hippocampal neurons and a reduction in GluA1 phosphorylation at Ser845. Reducing the ligand-independent activity of GHS-R1a increased the surface diffusion of AMPA receptors and impaired AMPA receptor–dependent synaptic delivery induced by chemical long-term potentiation. Accordingly, we found that blocking this GHS-R1a activity impaired spatial and recognition memory in mice. These observations support a role for the ligand-independent activity of GHS-R1a in regulating AMPA receptor trafficking under basal conditions and in the context of synaptic plasticity that underlies learning.

scholarly journals MDGAs are fast-diffusing molecules that delay excitatory synapse development by altering neuroligin behavior

2021 ◽  
Author(s):  
Andrea Toledo ◽  
Giorgia Bimbi ◽  
Mathieu Letellier ◽  
Beatrice Tessier ◽  
Sophie Daburon ◽  
...  
Keyword(s):  
Single Molecule ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Cellular Localization ◽  
Excitatory Synapses ◽  
Synapse Development ◽  
Membrane Diffusion ◽  
Single Molecule Tracking ◽  
Membrane Immobilization ◽  
In Cis

MDGAs are molecules that can bind neuroligins in cis and interfere with trans-synaptic neurexin-neuroligin interactions, thereby impairing synapse development. However, the sub-cellular localization and dynamics of MDGAs, as well as their specific mode of action in neurons are still unclear. Here, using both surface immunostaining of endogenous MDGAs and single molecule tracking of recombinant MDGAs in dissociated hippocampal neurons, we show that MDGA1 and MDGA2 molecules are homogeneously distributed and exhibit fast membrane diffusion, with a small reduction in mobility across neuronal maturation in culture Using shRNAs and CRISPR/Cas9 strategies to knock-down/out MDGA1 or MDGA2, we demonstrate an increase in the density of excitatory synapses accompanied by enhanced membrane immobilization and an increase in the phosphotyrosine level of neuroligins associated with excitatory post-synaptic differentiation. Finally, we show that decreasing MDGA expression level reduces the mobility of AMPA receptors and increases the frequency of AMPA receptor mediated mEPSCs. Overall, our results support a mechanism by which interactions between MDGAs and neuroligin-1 delays the assembly of functional excitatory synapses containing AMPA receptors.

scholarly journals Sr2+ and quantal events at excitatory synapses between mouse hippocampal neurons in culture.

1996 ◽  
Vol 495 (1) ◽  
pp. 113-125 ◽  
Author(s):  
M A Abdul-Ghani ◽  
T A Valiante ◽  
P S Pennefather
Keyword(s):  
Hippocampal Neurons ◽  
Excitatory Synapses

Molecular Basis for Functional Differences of AMPA-Subtype Glutamate Receptors

Physiology ◽  
1996 ◽  
Vol 11 (2) ◽  
pp. 77-82 ◽  
Author(s):  
S Ozawa ◽  
J Rossier
Keyword(s):  
Polymerase Chain Reaction ◽  
Ampa Receptors ◽  
Molecular Basis ◽  
Hippocampal Neurons ◽  
Polymerase Chain Reaction Amplification ◽  
Inward Rectification ◽  
Chain Reaction ◽  
Functional Differences ◽  
Reaction Amplification ◽  
Polymerase Chain

To trace the molecular basis of functional properties of native a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, we have coupled patch-clamp recordings and reverse transcription followed by polymerase chain reaction amplification. AMPA receptors lacking the GluR2 subunit in a population of hippocampal neurons exhibited a strong inward rectification and were highly permeable to Ca2+.

Electrophysiological evidence from glutamate microapplications for local excitatory circuits in the CA1 area of rat hippocampal slices

1988 ◽  
Vol 59 (1) ◽  
pp. 110-123 ◽  
Author(s):  
E. P. Christian ◽  
F. E. Dudek
Keyword(s):  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Recording Site ◽  
Postsynaptic Potentials ◽  
Inhibitory Postsynaptic Potentials ◽  
Ca1 Area ◽  
Transverse Slice

1. Evidence for local excitatory synaptic connections in CA1 of the rat hippocampus was obtained by recording excitatory postsynaptic potentials (EPSPs) intracellularly from pyramidal cells during local microapplications of glutamate. 2. Experiments were performed in hippocampal slices cut parallel to (transverse slice) or perpendicular to (longitudinal slice) alvear fibers. In normal solutions, glutamate microdrops (10–20 mM, 10–20 micron diam) applied in CA1 within 400 micron of recorded cells sometimes increased the frequency of inhibitory postsynaptic potentials for 5–10 s in both transverse and longitudinal slices. Increases in EPSP frequency were also occasionally observed, but only in transverse slices. Tetrodotoxin (1 microgram/ml) blocked glutamate-induced increases in PSP frequency, thus indicating that they were not caused by subthreshold effects on presynaptic terminals. Increases in PSP frequency were interpreted to result from glutamate activation of hippocampal neurons with inhibitory and excitatory connections to recorded neurons. 3. In both slice orientations, local excitatory circuits were studied in more isolated conditions by surgically separating CA1 from CA3 (transverse slices) and by blocking GABAergic inhibitory synapses with picrotoxin (5–10 microM). Microdrops were systematically applied at 200 and 400 micron on each side of the recording site. Significant glutamate-induced increases in EPSP frequency were observed in neurons from both slice orientations to microdrops in at least one of the locations. This provided evidence that excitatory synapses are present in both transverse and longitudinal slices. 4. Substantial increases in EPSP frequency only occurred in neurons from longitudinal slices when glutamate was microapplied 200 micron or less from the recording site. In transverse slices, however, large increases in EPSP frequency were observed to glutamate microapplications at 200 or 400 micron. These data suggest that CA1 local excitatory connections project for longer distances in the transverse than in the longitudinal plane of section. 5. Increases in EPSP frequency, averaged across cells, did not differ significantly in the four microapplication sites in either transverse or longitudinal slices. Thus local excitation in CA1 does not appear to be asymmetrically arranged in the way suggested for CA3. 6. The densities of local excitatory circuits in CA1 versus CA3 were studied by quantitatively comparing glutamate-induced increases in EPSP frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

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