Using Sterol Substitution to Probe the Role of Membrane Domains in Membrane Functions

Kim, Jihyun; London, Erwin

doi:10.1007/s11745-015-4007-y

Cited by 14 publications

(12 citation statements)

References 98 publications

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“…Similarly, structural differences in various sterol structures, such as the 3-hydroxyl group, the location of double bonds, aliphatic side chain, and flatness, can all affect the membrane biophysical properties and membrane order (17). Although ergosterol is the major membrane sterol in fungi, recruitment of altered sterol intermediates (minor sterols) into the membrane could significantly alter membrane order (84). Considering the fact that GlcCer(d19:2/18:0h) and several sterol structures are the most argued lipids for their role in virulence, in vitro studies using synthetic vesicles may shed light on their role in membrane physical properties (84)(85)(86)(87).…”

Section: Comparative Analysis Of Glccer and Sterols Of Other Cryptocomentioning

confidence: 99%

Analysis of sphingolipids, sterols, and phospholipids in human pathogenic Cryptococcus strains

Singh

MacKenzie

Girnun

et al. 2017

Journal of Lipid Research

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species cause invasive infections in humans. Lipids play an important role in the progression of these infections. Independent studies done by our group and others provide some detail about the functions of these lipids in infections. However, the pathways of biosynthesis and the metabolism of these lipids are not completely understood. To thoroughly understand the physiological role of these lipids, a proper structure and composition analysis of lipids is demanded. In this study, a detailed spectroscopic analysis of lipid extracts from and strains is presented. Sphingolipid profiling by LC-ESI-MS/MS was used to analyze sphingosine, dihydrosphingosine, sphingosine-1-phosphate, dihydrosphingosine-1-phosphate, ceramide, dihydroceramide, glucosylceramide, phytosphingosine, phytosphingosine-1-phosphate, phytoceramide, α-hydroxy phytoceramide, and inositolphosphorylceramide species. A total of 13 sterol species were identified using GC-MS, where ergosterol is the most abundant species. TheP-NMR-based phospholipid analysis identified phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidyl-,-dimethylethanolamine, phosphatidyl--monomethylethanolamine, phosphatidylglycerol, phosphatidic acid, and lysophosphatidylethanolamine. A comparison of lipid profiles among different strains illustrates a marked change in the metabolic flux of these organisms, especially sphingolipid metabolism. These data improve our understanding of the structure, biosynthesis, and metabolism of common lipid groups of and should be useful while studying their functional significance and designing therapeutic interventions.

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Section: Comparative Analysis Of Glccer and Sterols Of Other Cryptocomentioning

confidence: 99%

Analysis of sphingolipids, sterols, and phospholipids in human pathogenic Cryptococcus strains

Singh

MacKenzie

Girnun

et al. 2017

Journal of Lipid Research

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“…By sterol substitution, sterol structure and membrane properties can be varied under conditions such that total membrane lipid is more-or-less constant. This raises the possibility that replacing membrane cholesterol with different sterols might define when ordered domains are involved in biological functions (Xu and London, 2000), and a number of such studies have been carried out (as recently reviewed Kim and London, 2015). There are several ways to alter membrane sterol without changing sterol levels.…”

Section: Introductionmentioning

confidence: 99%

The effect of sterol structure upon clathrin-mediated and clathrin-independent endocytosis

Kim

Singh

Poeta

et al. 2017

Journal of Cell Science

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Ordered lipid domains (rafts) in plasma membranes have been hypothesized to participate in endocytosis based on inhibition of endocytosis by removal or sequestration of cholesterol. To more carefully investigate the role of the sterol in endocytosis, we used a substitution strategy to replace cholesterol with sterols that show various raft-forming abilities and chemical structures. Both clathrin-mediated endocytosis of transferrin and clathrin-independent endocytosis of clustered placental alkaline phosphatase were measured. A subset of sterols reversibly inhibited both clathrin-dependent and clathrin-independent endocytosis. The ability of a sterol to support lipid raft formation was necessary for endocytosis. However, it was not sufficient, because a sterol lacking a 3β-OH group did not support endocytosis even though it had the ability to support ordered domain formation. Double bonds in the sterol rings and an aliphatic tail structure identical to that of cholesterol were neither necessary nor sufficient to support endocytosis. This study shows that substitution using a large number of sterols can define the role of sterol structure in cellular functions. Hypotheses for how sterol structure can similarly alter clathrin-dependent and clathrin-independent endocytosis are discussed.

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“…In addition, dps Δ was more sensitive than the wild type to AmB and rarely grew in the presence of 2 μg/ml AmB ( Figure 4B ). The data demonstrated that the growth status of dps Δ worsened under external stress, which may be due to a disruption of the sterol biosynthesis pathway ( Kim and London, 2015 ; Gold et al, 2016 ).…”

Section: Resultsmentioning

confidence: 95%

“…Sterols have been extensively studied because of their important roles in drug resistance, developmental regulation, cell signaling, and cell growth. Therefore, a large number of sterols isolated from bacteria, fungi, and plants have been reported and researched ( Kim and London, 2015 ; Lamberson et al, 2017 ; Rivas-Marin et al, 2019 ; Ruan et al, 2019 ). Some sterols have even been implicated in human diseases, including Alzheimer’s disease and cancers ( Liu Z. et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

A Fungal Diterpene Synthase Is Responsible for Sterol Biosynthesis for Growth

et al. 2020

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A conserved open reading frame, dps , is described in Pestalotiopsis microspora , sharing a remarkable similarity with fungal diterpene synthases whose function is less studied. Loss-of-function approach manifested that dps was necessary for the growth and the development of the fungus. A deletion strain, dps Δ, showed a fundamental retardation in growth, which could deliberately be restored by the addition of exogenous sterols to the media. Gas chromatography–mass spectrometry analysis confirmed the loss of the ability to produce certain sterols. Thus, the tolerance and the resistance of dps Δ to several stress conditions were impaired. Secondary metabolites, such as the polyketide derivative dibenzodioxocinones, were significantly diminished. At the molecular level, the deletion of dps even affected the expression of genes in the mevalonate pathway. This report adds knowledge about fungal diterpene synthases in Pestalitiopsis microspora .

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Using Sterol Substitution to Probe the Role of Membrane Domains in Membrane Functions

Cited by 14 publications

References 98 publications

Analysis of sphingolipids, sterols, and phospholipids in human pathogenic Cryptococcus strains

Analysis of sphingolipids, sterols, and phospholipids in human pathogenic Cryptococcus strains

The effect of sterol structure upon clathrin-mediated and clathrin-independent endocytosis

A Fungal Diterpene Synthase Is Responsible for Sterol Biosynthesis for Growth

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