Membrane lipid rafts are required for AMPA receptor tyrosine phosphorylation

Hayashi, Takashi

doi:10.3389/fnsyn.2022.921772

Cited by 6 publications

(7 citation statements)

References 57 publications

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“…The objective of this review is to provide a comprehensive exploration and integrative analysis of information, suggesting the existence of lipid/protein-domain subtypes within neuronal cells. Several proteins that play major roles in neuronal calcium signaling have been described as components of lipid membrane domains [58], i.e., neurotransmitter receptors [59,60] and calcium transport systems [43,61], and they present a differential subcellular distribution within a single neuron and across different types of neurons, as shown in this review. The distribution pattern serves as a crucial tool for proposing the existence of diverse lipid membrane-domain subtypes in neurons.…”

Section: Lipid Membrane Nanodomains Organization In the Neuronal Plas...mentioning

confidence: 89%

Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?

Samhan-Arias,

Poejo,

Marques-da-Silva

et al. 2023

Molecules

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Lipid membrane nanodomains or lipid rafts are 10–200 nm diameter size cholesterol- and sphingolipid-enriched domains of the plasma membrane, gathering many proteins with different roles. Isolation and characterization of plasma membrane proteins by differential centrifugation and proteomic studies have revealed a remarkable diversity of proteins in these domains. The limited size of the lipid membrane nanodomain challenges the simple possibility that all of them can coexist within the same lipid membrane domain. As caveolin-1, flotillin isoforms and gangliosides are currently used as neuronal lipid membrane nanodomain markers, we first analyzed the structural features of these components forming nanodomains at the plasma membrane since they are relevant for building supramolecular complexes constituted by these molecular signatures. Among the proteins associated with neuronal lipid membrane nanodomains, there are a large number of proteins that play major roles in calcium signaling, such as ionotropic and metabotropic receptors for neurotransmitters, calcium channels, and calcium pumps. This review highlights a large variation between the calcium signaling proteins that have been reported to be associated with isolated caveolin-1 and flotillin-lipid membrane nanodomains. Since these calcium signaling proteins are scattered in different locations of the neuronal plasma membrane, i.e., in presynapses, postsynapses, axonal or dendritic trees, or in the neuronal soma, our analysis suggests that different lipid membrane-domain subtypes should exist in neurons. Furthermore, we conclude that classification of lipid membrane domains by their content in calcium signaling proteins sheds light on the roles of these domains for neuronal activities that are dependent upon the intracellular calcium concentration. Some examples described in this review include the synaptic and metabolic activity, secretion of neurotransmitters and neuromodulators, neuronal excitability (long-term potentiation and long-term depression), axonal and dendritic growth but also neuronal cell survival and death.

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Section: Lipid Membrane Nanodomains Organization In the Neuronal Plas...mentioning

confidence: 89%

Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?

Samhan-Arias,

Poejo,

Marques-da-Silva

et al. 2023

Molecules

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Section: Introductionmentioning

confidence: 90%

“…24,27,28 Moreover, cholesterol has been implicated in the localization and trafficking of mGluRs, with cholesterol-rich lipid rafts serving as platforms for mGluR signaling complexes. 16,[29][30][31][32] These findings suggest a potential role for lipid-protein interactions in fine tuning mGluR signaling. Despite these insights, the molecular mechanisms underlying cholesterol-dependent modulation of mGluRs, particularly mGluR1, remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol Dependence of the Conformational Changes in Metabotropic Glutamate Receptor 1

Isu,

Badiee,

Polasa

et al. 2024

Preprint

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Metabotropic glutamate receptors (mGluRs) are class C G protein-coupled receptors that function as obligate dimers in regulating neurotransmission and synaptic plasticity in the central nervous system. The mGluR1 subtype has been shown to be modulated by the membrane lipid environment, particularly cholesterol, though the molecular mechanisms remain elusive. In this study, we employed all-atom molecular dynamics simulations to investigate the effects of cholesterol on the conformational dynamics of the mGluR1 seven transmembrane (7TM) domain in an inactive state model. Simulations were performed with three di erent cholesterol concentrations (0%, 10%, and 25%) in a palmitoyl-oleoyl phosphatidylcholine (POPC) lipid bilayer system. Our results demonstrate that cholesterol induces conformational changes in the mGluR1 dimer more significantly than in the individual protomers. Notably, cholesterol modulates the dynamics and conformations of the TM1 and TM2 helices at the dimer interface. Interestingly, an intermediate cholesterol concentration of 10% elicits more pronounced conformational changes compared to both cholesterol-depleted (0%) and cholesterol-enriched (25%) systems. Specific electrostatic interaction unique to the 10% cholesterol system further corroborate these conformational differences. Given the high sequence conservation of the 7TM domains across mGluR subtypes, the cholesterol-dependent effects observed in mGluR1 are likely applicable to other members of this receptor family. Our findings provide atomistic insights into how cholesterol modulates the conformational landscape of mGluRs, which could impact their function and signaling mechanisms.

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“…Lipid rafts also modulate the activity and signalling of synaptic proteins by affecting their interactions with other molecules, such as ligands, kinases and phosphatases [ 13 , 124 ]. A decrease in cholesterol and sphingolipid levels results in the destabilisation of surface AMPA receptors and a progressive decline in both inhibitory and excitatory synapses, along with dendritic spines [ 125 ]. In raft-depleted neurons [ 116 ], the remaining synapses and spines exhibit significant enlargement.…”

Section: Role Of Lipid Rafts In Brain Developmentmentioning

confidence: 99%

“…Both receptors and their association with lipid rafts are necessary for the formation of stable synapses. It is important to have a tool that is capable of rapidly monitoring the formation, disruption or enhancement of synapse formation, and densely seeded primary neuronal cell cultures provide this tool [ 122 , 125 , 239 , 240 ].…”

Section: In Vitro Neural Cell Culture—model To Study Role Of Lipid Ra...mentioning

confidence: 99%

Lipid Rafts: The Maestros of Normal Brain Development

Viljetić,

Blažetić,

Labak

et al. 2024

Biomolecules

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Lipid rafts, specialised microdomains within cell membranes, play a central role in orchestrating various aspects of neurodevelopment, ranging from neural differentiation to the formation of functional neuronal networks. This review focuses on the multifaceted involvement of lipid rafts in key neurodevelopmental processes, including neural differentiation, synaptogenesis and myelination. Through the spatial organisation of signalling components, lipid rafts facilitate precise signalling events that determine neural fate during embryonic development and in adulthood. The evolutionary conservation of lipid rafts underscores their fundamental importance for the structural and functional complexity of the nervous system in all species. Furthermore, there is increasing evidence that environmental factors can modulate the composition and function of lipid rafts and influence neurodevelopmental processes. Understanding the intricate interplay between lipid rafts and neurodevelopment not only sheds light on the fundamental mechanisms governing brain development but also has implications for therapeutic strategies aimed at cultivating neuronal networks and addressing neurodevelopmental disorders.

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Membrane lipid rafts are required for AMPA receptor tyrosine phosphorylation

Cited by 6 publications

References 57 publications

Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?

Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?

Cholesterol Dependence of the Conformational Changes in Metabotropic Glutamate Receptor 1

Lipid Rafts: The Maestros of Normal Brain Development

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