Recent Findings on AMPA Receptor Recycling

Moretto, Edoardo; Passafaro, Maria

doi:10.3389/fncel.2018.00286

Cited by 30 publications

(26 citation statements)

References 127 publications

(169 reference statements)

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“…GluA1 is calcium-permeable (without GluA2) and is associated with LTP (long-term potentiation) [16] and LTD (long-term depression) [10], which affect the synaptic plasticity. Due to its abundance in the human brain, its up- and downregulation have been shown to influence the neuronal function in various diseases [17].…”

Section: Introductionmentioning

confidence: 99%

The Neuroprotective Role of Origanum syriacum L. and Lavandula dentata L. Essential Oils through Their Effects on AMPA Receptors

Qneibi

Jaradat

Hawash

et al. 2019

BioMed Research International

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Lavandula dentata L. and Origanum syriacum L. essential oils have numerous health benefits and properties, such as possessing common components with a variant degree of depressive actions in the central nervous system. We investigated the depressive property of these oils on AMPA receptors, which are responsible for most of the fast-excitatory neurotransmission in the CNS and play a critical role in synaptic plasticity. Since excessive activation of AMPARs has been linked to neurotoxicity leading to various pathologies, we hypothesize that these oils have a neuroprotective role by acting directly on the kinetics of AMPARs. Using Gas Chromatography-Mass Spectrometry (GC/MS) and patch-clamp electrophysiology, the essential oils of L. dentata flowers and O. syriacum leaves were characterized and the whole cell currents were measured with and without the administration of the oils onto HEK293 cells. The current study results showed that the biophysical properties of AMPA receptor subunits showed a decrease in desensitization rate of GluA1 and GluA2 homomers, using O. syriacum, while administering L. dentata oil decreased the desensitization rate of GluA1 and GluA2 homomers, as well as GluA1/2 heteromers. As for the deactivation rate, both oils slowed the deactivation kinetics of all AMPA receptor subunits. Intriguingly, between the two oils, the effect of desensitization and deactivation was of a greater significance for L. dentata oil than O. syriacum. Our data suggest that the two oils contain components that are essential to identify, as those active components underlie the oils’ neuronal depressive properties reported, and to extract them to synthesize a potent neuroprotective drug to treat neurological diseases potentially.

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Section: Introductionmentioning

confidence: 99%

The Neuroprotective Role of Origanum syriacum L. and Lavandula dentata L. Essential Oils through Their Effects on AMPA Receptors

Qneibi

Jaradat

Hawash

et al. 2019

BioMed Research International

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“…First, it is widely believed that AMPAR tetramers with various subunit compositions are fully and stably assembled in the endoplasmic reticulum (ER) 12,13 , and then the stable tetramers are carried to the vesicular pool near the plasma membrane (PM), as well as to the PM itself and to the postsynaptic membrane, by vesicular trafficking and lateral diffusion 11,14,15 . In fact, AMPAR tetramers formed in the ER are considered to be stable till their proteolytic decomposition 16 . It follows then that for tuning the number and subunit compositions of AMPAR in the postsynaptic membrane, the tetramers with different subunit compositions must be pooled in the ER or in the PM and carried to the postsynaptic membrane 8,11 , suggesting that the pool must be quite large.…”

Section: Introductionmentioning

confidence: 99%

AMPA receptors in the synapse turnover by monomer diffusion

et al. 2019

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The number and subunit compositions of AMPA receptors (AMPARs), hetero- or homotetramers composed of four subunits GluA1–4, in the synapse is carefully tuned to sustain basic synaptic activity. This enables stimulation-induced synaptic plasticity, which is central to learning and memory. The AMPAR tetramers have been widely believed to be stable from their formation in the endoplasmic reticulum until their proteolytic decomposition. However, by observing GluA1 and GluA2 at the level of single molecules, we find that the homo- and heterotetramers are metastable, instantaneously falling apart into monomers, dimers, or trimers (in 100 and 200 ms, respectively), which readily form tetramers again. In the dendritic plasma membrane, GluA1 and GluA2 monomers and dimers are far more mobile than tetramers and enter and exit from the synaptic regions. We conclude that AMPAR turnover by lateral diffusion, essential for sustaining synaptic function, is largely done by monomers of AMPAR subunits, rather than preformed tetramers.

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“…S21a). This suggests that at high ligand concentrations, the internalization of AMPAR, a well-established phenomenon, 65 likely occurs. The ligand-free control probe 22, loaded at high concentration which leads to non-specific membrane labeling (1 μM, 2 h), also partially attenuated sEPSC frequency (Fig.…”

Section: Dextran Is Compatible With Ligand-directed Acyl Imidazole Chmentioning

confidence: 97%

Chemical targeting of voltage sensitive dyes to specific cells and molecules in the brain

Fiala¹,

Wang²,

Dunn³

et al. 2020

Preprint

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Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. These sensors, rendered highly lipophilic to anchor the conjugated pi-wire molecular framework in the membrane, offer several favorable functional parameters including fast response kinetics and high sensitivity to membrane potential changes. The impact of VSDs has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a non-genetic molecular platform for cell- and molecule-specific targeting of synthetic voltage sensitive dyes in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of voltage sensitive dyes by dynamic encapsulation, and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. We envision that modularity of our platform will enable its application to a variety of molecular targets and sensors, as well as lipophilic drugs and signaling modulators. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.

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Recent Findings on AMPA Receptor Recycling

Cited by 30 publications

References 127 publications

The Neuroprotective Role of Origanum syriacum L. and Lavandula dentata L. Essential Oils through Their Effects on AMPA Receptors

The Neuroprotective Role of Origanum syriacum L. and Lavandula dentata L. Essential Oils through Their Effects on AMPA Receptors

AMPA receptors in the synapse turnover by monomer diffusion

Chemical targeting of voltage sensitive dyes to specific cells and molecules in the brain

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