Lipid Regulation of Receptor Function

Fantini, Jacques; Yahi, Nouara

doi:10.1016/b978-0-12-800111-0.00007-2

Cited by 10 publications

(6 citation statements)

References 98 publications

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“…In 2015, Fantini reported on the presence of a GM1-binding domain in the extracellular domain of Trk receptor, suggesting that GM1 oligosaccharide could act as an endogenous activator of Trk receptor [196]. Recently we added more details on the molecular basis of the GM1-TrkA interaction.…”

Section: Oligogm1 and Trka Interaction Study In Silicomentioning

confidence: 99%

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

Chiricozzi

Lunghi

Biase

et al. 2020

IJMS

102

140

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Many species of ganglioside GM1, differing for the sialic acid and ceramide content, have been characterized and their physico-chemical properties have been studied in detail since 1963. Scientists were immediately attracted to the GM1 molecule and have carried on an ever-increasing number of studies to understand its binding properties and its neurotrophic and neuroprotective role. GM1 displays a well balanced amphiphilic behavior that allows to establish strong both hydrophobic and hydrophilic interactions. The peculiar structure of GM1 reduces the fluidity of the plasma membrane which implies a retention and enrichment of the ganglioside in specific membrane domains called lipid rafts. The dynamism of the GM1 oligosaccharide head allows it to assume different conformations and, in this way, to interact through hydrogen or ionic bonds with a wide range of membrane receptors as well as with extracellular ligands. After more than 60 years of studies, it is a milestone that GM1 is one of the main actors in determining the neuronal functions that allows humans to have an intellectual life. The progressive reduction of its biosynthesis along the lifespan is being considered as one of the causes underlying neuronal loss in aged people and severe neuronal decline in neurodegenerative diseases. In this review, we report on the main knowledge on ganglioside GM1, with an emphasis on the recent discoveries about its bioactive component.

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Section: Oligogm1 and Trka Interaction Study In Silicomentioning

confidence: 99%

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

Chiricozzi

Lunghi

Biase

et al. 2020

IJMS

102

140

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“…Regulation of sphingolipid metabolite signaling likely involves segregating the parent sphingolipid molecules within distinct plasma membrane domains, but the distributions of various sphingolipids within the plasma membrane are not well established. At present, the different subspecies within the sphingolipid family are known to vary in terms of their chemical properties, expression patterns, specific protein binding partners, and consequently, specialized functions (Hannun and Bell, 1989; Mutoh et al, 1995; Snook et al, 2006; Yu et al, 2011; Contreras et al, 2012; Fantini and Yahi, 2015; Prasanna et al, 2016). These divergent properties and functions may suggest that each sphingolipid subspecies is compartmentalized within a different region of the plasma membrane.…”

Section: Introductionmentioning

confidence: 99%

Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It

Kraft

2017

Front. Cell Dev. Biol.

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Sphingolipids are structural components in the plasma membranes of eukaryotic cells. Their metabolism produces bioactive signaling molecules that modulate fundamental cellular processes. The segregation of sphingolipids into distinct membrane domains is likely essential for cellular function. This review presents the early studies of sphingolipid distribution in the plasma membranes of mammalian cells that shaped the most popular current model of plasma membrane organization. The results of traditional imaging studies of sphingolipid distribution in stimulated and resting cells are described. These data are compared with recent results obtained with advanced imaging techniques, including super-resolution fluorescence detection and high-resolution secondary ion mass spectrometry (SIMS). Emphasis is placed on the new insight into the sphingolipid organization within the plasma membrane that has resulted from the direct imaging of stable isotope-labeled lipids in actual cell membranes with high-resolution SIMS. Super-resolution fluorescence techniques have recently revealed the biophysical behaviors of sphingolipids and the unhindered diffusion of cholesterol analogs in the membranes of living cells are ultimately in contrast to the prevailing hypothetical model of plasma membrane organization. High-resolution SIMS studies also conflicted with the prevailing hypothesis, showing sphingolipids are concentrated in micrometer-scale membrane domains, but cholesterol is evenly distributed within the plasma membrane. Reductions in cellular cholesterol decreased the number of sphingolipid domains in the plasma membrane, whereas disruption of the cytoskeleton eliminated them. In addition, hemagglutinin, a transmembrane protein that is thought to be a putative raft marker, did not cluster within sphingolipid-enriched regions in the plasma membrane. Thus, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with cholesterol or hemagglutinin. The alternate views of plasma membrane organization suggested by these findings are discussed.

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“…Lipid rafts are characterized by lipid and protein heterogeneity [53], and are dynamic structures capable of floating on the cell surface. In addition, their lipid pattern and organization are strongly influenced by the variation of a single component [58].…”

Section: Lipid‐raft Dynamicsmentioning

confidence: 99%

“…TrkA is a transmembrane protein receptor with a cytosolic moiety (comprising the autophosphorylation site), a transmembrane hydrophobic portion, and a hydrophilic extracellular region. TrkA and GM1 bind with their respective extracellular portions [53] as demonstrated through photolabelling experiments: using GM1 derivatives with photoactivatable groups associated with the oligosaccharide head or to the ceramide tail, it was demonstrated that GM1 directly binds TrkA through its oligosaccharide [54,55]. In accordance, bioinformatics data obtained from the crystallized portion of TrkA relative to its hydrophilic extracellular domain showed that the GM1 oligosaccharide fits into a "pocket" formed by the TrkA-NGF complex, acting as a bridge capable of stabilizing the complex [56,57].…”

Section: Gm1 Positively Modulates Ngf Receptor Activitymentioning

confidence: 99%

Regulation of signal transduction by gangliosides in lipid rafts: focus on GM3–IR and GM1–TrkA interactions

et al. 2022

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The interactions between gangliosides and proteins belonging to the same or different lipid domains and their influence on physiological and pathological states have been analysed in detail. A well-known factor impacting on lipidprotein interactions and their biological outcomes is the dynamic composition of plasma membrane. This review focuses on GM1 and GM3 gangliosides because they are an integral part of protein-receptor complexes and dysregulation of their concentration shows a direct correlation with the onset of pathological conditions. We first discuss the interaction between GM3 and insulin receptor in relation to insulin responses, with an increase in GM3 correlating with the onset of metabolic dysfunction. Next, we describe the case of the GM1-TrkA interaction, relevant to nerve-cell differentiation and homeostasis as deficiency in plasma-membrane GM1 is known to promote neurodegeneration. These two examples highlight the fact that interactions between gangliosides and receptor proteins within the plasma membrane are crucial in controlling cell signalling and pathophysiological cellular states.

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Lipid Regulation of Receptor Function

Cited by 10 publications

References 98 publications

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It

Regulation of signal transduction by gangliosides in lipid rafts: focus on GM3–IR and GM1–TrkA interactions

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