Determination of the size of lipid rafts studied through single-molecule FRET simulations

Hernández-Adame, Pablo Luis; Meza, Ulises; Rodríguez-Menchaca, Aldo A.; Sánchez‐Armass, Sergio; Ruíz-García, Jaime; Gomez, E.

doi:10.1016/j.bpj.2021.04.003

Cited by 7 publications

(5 citation statements)

References 49 publications

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“…Nanoscale domains of clustered proteins, lipids and other molecules in cell membranes play many important roles in signaling and trafficking 66 . Referred to as Lipid Rafts, these important membrane subdomains span a large range of sizes, reported as 10 nm to 200 nm in a definition that includes caveola 67 , although a recent fluorescence resonance energy transfer study measured a lower bound of 5 nm 68 . Lipid rafts are dynamic in their molecular composition, and may be mobile and diffuse freely in the membrane or become bound to cytoskeleton and immobile 69 .…”

Section: Resultsmentioning

confidence: 99%

Vesicle and reaction-diffusion hybrid modeling with STEPS

Hepburn,

Lallouette,

Chen

et al. 2024

Commun Biol

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Vesicles carry out many essential functions within cells through the processes of endocytosis, exocytosis, and passive and active transport. This includes transporting and delivering molecules between different parts of the cell, and storing and releasing neurotransmitters in neurons. To date, computational simulation of these key biological players has been rather limited and has not advanced at the same pace as other aspects of cell modeling, restricting the realism of computational models. We describe a general vesicle modeling tool that has been designed for wide application to a variety of cell models, implemented within our software STochastic Engine for Pathway Simulation (STEPS), a stochastic reaction-diffusion simulator that supports realistic reconstructions of cell tissue in tetrahedral meshes. The implementation is validated in an extensive test suite, parallel performance is demonstrated in a realistic synaptic bouton model, and example models are visualized in a Blender extension module.

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Section: Resultsmentioning

confidence: 99%

Vesicle and reaction-diffusion hybrid modeling with STEPS

Hepburn,

Lallouette,

Chen

et al. 2024

Commun Biol

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“…The existence lipid rafts was initially a subject of debate between physical chemists and histologists due to difficulties in visualizing them and their illdefined molecular composition [1,2]. In the last two decades, a number of new techniques such as single-molecule spectroscopy, super-resolution microscopy, fluorescence recovery after photobleaching, stimulated emission depletion, Förster resonance energy transfer (FRET), total internal reflection fluorescence, and fluorescence correlation spectroscopy techniques allowed to estimate the lower limit of lipid rafts in <20 nm [3][4][5][6]. Plasma membrane domains of 26 ± 13 nm radius have been observed in living cells diffusing as one entity for minutes [7].…”

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

confidence: 99%

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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“…GPMVs retain membrane lipid and protein diversity, and are capable of phase separation but only form optically resolvable lipid rafts at low temperatures of up to 20 • C [62]. More advanced techniques such as fluorescence resonance energy transfer have now allowed for the analysis of smaller rafts at physiological temperatures [63,64].…”

Section: Biological Function Of Ceramide and Sphingomyelinmentioning

confidence: 99%

The Role of Sphingomyelin and Ceramide in Motor Neuron Diseases

McCluskey

Donaghy

Morrison

et al. 2022

JPM

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Amyotrophic Lateral Sclerosis (ALS), Spinal Bulbar Muscular Atrophy (SBMA), and Spinal Muscular Atrophy (SMA) are motor neuron diseases (MNDs) characterised by progressive motor neuron degeneration, weakness and muscular atrophy. Lipid dysregulation is well recognised in each of these conditions and occurs prior to neurodegeneration. Several lipid markers have been shown to predict prognosis in ALS. Sphingolipids are complex lipids enriched in the central nervous system and are integral to key cellular functions including membrane stability and signalling pathways, as well as being mediators of neuroinflammation and neurodegeneration. This review highlights the metabolism of sphingomyelin (SM), the most abundant sphingolipid, and of its metabolite ceramide, and its role in the pathophysiology of neurodegeneration, focusing on MNDs. We also review published lipidomic studies in MNDs. In the 13 studies of patients with ALS, 12 demonstrated upregulation of multiple SM species and 6 demonstrated upregulation of ceramides. SM species also correlated with markers of clinical progression in five of six studies. These data highlight the potential use of SM and ceramide as biomarkers in ALS. Finally, we review potential therapeutic strategies for targeting sphingolipid metabolism in neurodegeneration.

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Determination of the size of lipid rafts studied through single-molecule FRET simulations

Cited by 7 publications

References 49 publications

Vesicle and reaction-diffusion hybrid modeling with STEPS

Vesicle and reaction-diffusion hybrid modeling with STEPS

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

The Role of Sphingomyelin and Ceramide in Motor Neuron Diseases

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