GM1 Ganglioside role in the interaction of Alpha-synuclein with lipid membranes: Morphology and structure

Perissinotto, Fabio; Rondelli, Valeria; Parisse, Pietro; Tormena, N.; Zunino, Alessandro; Almásy, László; Merkel, D. G.; Bottyán, L.; Sajti, Sz.; Casalis, Loredana

doi:10.1016/j.bpc.2019.106272

Cited by 38 publications

(20 citation statements)

References 75 publications

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“…In addition, supported lipid bilayers composed of mixed PC and GM1 ganglioside were recently prepared in order to investigate the selective α-syn/GM1 interaction, which induced strong structural rearrangement of the biomimetic membranes (Figure 3a). This observation is a strong indication of the potential critical role of lipid rafts in the biological function of α-syn [97].…”

Section: Protein-lipid Interactionsmentioning

confidence: 70%

“…We also discussed some recent applications of the biomimetic lipid membranes for the characterization of their interaction with proteins, as well as drugs (Section 3). In particular, these studies showed the great functional role of lipid rafts in biological interactions at the membrane surface [97,101,113].…”

Section: Discussionmentioning

confidence: 98%

“…Neutron reflectometry measurements revealed that GM1 affects the location of α-syn with respect to the biomimetic lipid membrane. Adapted and reprinted with permission from [97], Copyright (2019) Elsevier. (b) Schematic representation of the interaction between the gH625 fusion peptide from the envelope of the herpes simplex virus (HSV) and lipid vesicles with lipid composition mimicking the rafts in the mammalian plasma membrane.…”

Section: Protein-lipid Interactionsmentioning

confidence: 99%

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Mimicking the Mammalian Plasma Membrane: An Overview of Lipid Membrane Models for Biophysical Studies

Luchini

Vitiello

2020

Biomimetics

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Cell membranes are very complex biological systems including a large variety of lipids and proteins. Therefore, they are difficult to extract and directly investigate with biophysical methods. For many decades, the characterization of simpler biomimetic lipid membranes, which contain only a few lipid species, provided important physico-chemical information on the most abundant lipid species in cell membranes. These studies described physical and chemical properties that are most likely similar to those of real cell membranes. Indeed, biomimetic lipid membranes can be easily prepared in the lab and are compatible with multiple biophysical techniques. Lipid phase transitions, the bilayer structure, the impact of cholesterol on the structure and dynamics of lipid bilayers, and the selective recognition of target lipids by proteins, peptides, and drugs are all examples of the detailed information about cell membranes obtained by the investigation of biomimetic lipid membranes. This review focuses specifically on the advances that were achieved during the last decade in the field of biomimetic lipid membranes mimicking the mammalian plasma membrane. In particular, we provide a description of the most common types of lipid membrane models used for biophysical characterization, i.e., lipid membranes in solution and on surfaces, as well as recent examples of their applications for the investigation of protein-lipid and drug-lipid interactions. Altogether, promising directions for future developments of biomimetic lipid membranes are the further implementation of natural lipid mixtures for the development of more biologically relevant lipid membranes, as well as the development of sample preparation protocols that enable the incorporation of membrane proteins in the biomimetic lipid membranes.

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Section: Protein-lipid Interactionsmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 98%

Section: Protein-lipid Interactionsmentioning

confidence: 99%

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Mimicking the Mammalian Plasma Membrane: An Overview of Lipid Membrane Models for Biophysical Studies

Luchini

Vitiello

2020

Biomimetics

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“…This may be problematic as polymerization of Aβ fibrils may disrupt extracellular trafficking and communication between cells. In contrast, GM1 oligosaccharides appear to prevent the aggregation of SNCA [79,82,147,148].…”

Section: Alzheimer's Diseasementioning

confidence: 87%

Metabolism of Glycosphingolipids and Their Role in the Pathophysiology of Lysosomal Storage Disorders

Ryckman

Brockhausen

Walia

2020

IJMS

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Glycosphingolipids (GSLs) are a specialized class of membrane lipids composed of a ceramide backbone and a carbohydrate-rich head group. GSLs populate lipid rafts of the cell membrane of eukaryotic cells, and serve important cellular functions including control of cell–cell signaling, signal transduction and cell recognition. Of the hundreds of unique GSL structures, anionic gangliosides are the most heavily implicated in the pathogenesis of lysosomal storage diseases (LSDs) such as Tay-Sachs and Sandhoff disease. Each LSD is characterized by the accumulation of GSLs in the lysosomes of neurons, which negatively interact with other intracellular molecules to culminate in cell death. In this review, we summarize the biosynthesis and degradation pathways of GSLs, discuss how aberrant GSL metabolism contributes to key features of LSD pathophysiology, draw parallels between LSDs and neurodegenerative proteinopathies such as Alzheimer’s and Parkinson’s disease and lastly, discuss possible therapies for patients.

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“…Here, the hydrophobic Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) domain is accredited for being essential in the membrane anchoring of the fulllength protein with the lipid membrane, leading to aggregation and packing of the acyl tails in the hydrophobic membrane core 20,21 . For cationic proteins such as tau and the N-terminal domain of α-synuclein, negativelycharged membrane surfaces drive electrostatic attraction between basic side chains in the protein and lipid head groups or gangliosides in the external membrane leaflet, facilitating the formation of toxic aggregates in situ at the membrane [22][23][24][25][26][27] . Likewise, prefibrillar assemblies of HypF-N were shown to preferentially permeabilise bilayers enriched in anionic phospholipids or glycolipids [28][29][30] .…”

mentioning

confidence: 99%

Toxic oligomers of the amyloidogenic HypF-N protein form pores in mitochondrial membranes

Farrugia

Caruana

Ghio

et al. 2020

Sci Rep

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Studies on the amyloidogenic N-terminal domain of the E. coli HypF protein (HypF-N) have contributed significantly to a detailed understanding of the pathogenic mechanisms in neurodegenerative diseases characterised by the formation of misfolded oligomers, by proteins such as amyloid-β, α-synuclein and tau. Given that both cell membranes and mitochondria are increasingly recognised as key targets of oligomer toxicity, we investigated the damaging effects of aggregates of HypF-N on mitochondrial membranes. Essentially, we found that HypF-N oligomers characterised by high surface hydrophobicity (type A) were able to trigger a robust permeabilisation of mito-mimetic liposomes possessing cardiolipin-rich membranes and dysfunction of isolated mitochondria, as demonstrated by a combination of mitochondrial shrinking, lowering of mitochondrial membrane potential and cytochrome c release. Furthermore, using single-channel electrophysiology recordings we obtained evidence that the type A aggregates induced currents reflecting formation of ion-conducting pores in mito-mimetic planar phospholipid bilayers, with multi-level conductances ranging in the hundreds of pS at negative membrane voltages. Conversely, HypF-N oligomers with low surface hydrophobicity (type B) could not permeabilise or porate mitochondrial membranes. These results suggest an inherent toxicity of membrane-active aggregates of amyloid-forming proteins to mitochondria, and that targeting of oligomer-mitochondrial membrane interactions might therefore afford protection against such damage.

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GM1 Ganglioside role in the interaction of Alpha-synuclein with lipid membranes: Morphology and structure

Cited by 38 publications

References 75 publications

Mimicking the Mammalian Plasma Membrane: An Overview of Lipid Membrane Models for Biophysical Studies

Mimicking the Mammalian Plasma Membrane: An Overview of Lipid Membrane Models for Biophysical Studies

Metabolism of Glycosphingolipids and Their Role in the Pathophysiology of Lysosomal Storage Disorders

Toxic oligomers of the amyloidogenic HypF-N protein form pores in mitochondrial membranes

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