Nanoscopic Spatial Association between Ras and Phosphatidylserine on the Cell Membrane Studied with Multicolor Super Resolution Microscopy

Koester, Anna M.; Tao, Kai; Szczepaniak, Malwina; Rames, Matthew J.; Nan, Xiaolin

doi:10.3390/biom12081033

Cited by 8 publications

(9 citation statements)

References 59 publications

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“…For instance, PS is the most abundant anionic phospholipid in mammalian cells [40]. Non-overlapping PS domains have been shown to exist in the cell PM [23,40,41]. PS has been shown to associate with the CHOL-independent KRAS4B nanoclusters in the PM (will be elaborated below, [23][24][25][26]42]).…”

Section: Phospholipids Laterally Segregate To Distinct Domains In Mem...mentioning

confidence: 99%

RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling

Zhou

Hancock

2023

FEBS Letters

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Mutations of rat sarcoma virus (RAS) oncogenes (HRAS, KRAS and NRAS) can contribute to the development of cancers and genetic disorders (RASopathies). The spatiotemporal organization of RAS is an important property that warrants further investigation. In order to function, wild-type or oncogenic mutants of RAS must be localized to the inner leaflet of the plasma membrane (PM), which is driven by interactions between their C-terminal membraneanchoring domains and PM lipids. The isoform-specific RAS-lipid interactions promote the formation of nanoclusters on the PM. As main sites for effector recruitment, these nanoclusters are biologically important. Since the spatial distribution of lipids is sensitive to changing environments, such as mechanical and electrical perturbations, RAS nanoclusters act as transducers to convert external stimuli to intracellular mitogenic signalling. As such, effective inhibition of RAS oncogenesis requires consideration of the complex interplay between RAS nanoclusters and various cell surface and extracellular stimuli. In this review, we discuss in detail how, by sorting specific lipids in the PM, RAS nanoclusters act as transducers to convert external stimuli into intracellular signalling.

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Section: Phospholipids Laterally Segregate To Distinct Domains In Mem...mentioning

confidence: 99%

RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling

Zhou

Hancock

2023

FEBS Letters

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“…Furthermore, Ras (small GTPase) nanoclustering has been shown to be important in oncogenic signalling and attempts to disrupt Ras nanoclusters are being explored as a potential therapeutic strategy ( Van et al, 2021 ). Several studies have identified Ras interaction with phosphatidylserine in membrane clustering, and a recent super-resolution microscopy study defined the nanoscopic spatial membrane association between Ras and phosphatidylserine ( Koester et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Location, location, location: Protein kinase nanoclustering for optimised signalling output

Gormal,

Martinez-Marmol,

Brooks

et al. 2024

eLife

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Protein kinases (PKs) are proteins at the core of cellular signalling and are thereby responsible for most cellular physiological processes and their regulations. As for all intracellular proteins, PKs are subjected to Brownian thermal energy that tends to homogenise their distribution throughout the volume of the cell. To access their substrates and perform their critical functions, PK localisation is therefore tightly regulated in space and time, relying upon a range of clustering mechanisms. These include post-translational modifications, protein–protein and protein–lipid interactions, as well as liquid–liquid phase separation, allowing spatial restriction and ultimately regulating access to their substrates. In this review, we will focus on key mechanisms mediating PK nanoclustering in physiological and pathophysiological processes. We propose that PK nanoclusters act as a cellular quantal unit of signalling output capable of integration and regulation in space and time. We will specifically outline the various super-resolution microscopy approaches currently used to elucidate the composition and mechanisms driving PK nanoscale clustering and explore the pathological consequences of altered kinase clustering in the context of neurodegenerative disorders, inflammation, and cancer.

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“…Saturated fatty acids with 16 or more carbons are often connected to the sn-1 position in PS, whereas unsaturated fatty acids are typically located at the sn-2 position, even though the acyl chains in PS differ among cell types and organelles [19,20]. PS makes up a small portion of most cellular membranes [21,22]. The PS has an important role in the removal of apoptotic cells.…”

Section: Introductionmentioning

confidence: 99%

Hydrolysis of Phospholipids in Presence of Phospholipase D:Thrmodynamic and Kinetic Studies of Hydrolysis in Water and Alcoholic Environments

S. Hussein,

M. M. Al-Rammahi

2024

ANJS

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Phospholipase D(PLD)catalyzes the hydrolysis of phospholipids to produce phosphatidic acid and hydroxyl compounds. Phosphatidylcholine (PC) is the most abundant phospholipid in animals and plants, often constituting nearly 50% of total complex lipids in animals and plants. However, Phosphatidylserine (PS) makes up around 5–10% of all phospholipids. This work includes the monitoring thermodynamic and kinetic of the enzymatic hydrolysis of PC and PS in both water and ethanol. All experiments were performedusing the Schlink line technique inN2present as an inert gas to prevent the oxidative stress. UV/Vis. spectrophotometer was used to observe the kinetic of all enzymatic reactions. In addition, the Origin 2019 software was used to analyze and find the kinetic parameters of the enzymatic hydrolysis reactions. The results show that the enzymatic hydrolys is reactions of PC in water and in ethanol occurredat the same conditions, enzymatic activity 1.752 U/mg, temperature 37 ᵒC, and pH =7. However, the enzymatic hydrolysis reactions of PS in water occurred at different conditions than in ethanol. The enzymatic substitution reaction of PSinethanol was thermodynamic favorable reaction due to the value of the ∆G =_164.868 J, but in water was thermodynamically unfavorable ΔG = 65.048 J. However, the enzymatic hydrolysis reaction of PC in water was thermodynamically unfavorable ∆G = 345.319 Jaswellas in ethanol ∆G = 74.433 J. The study shows that there is clear impact of present nitrogen bases of PC and the environment of the hydrolysis on the activity of the enzymatic catalyzing.

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Nanoscopic Spatial Association between Ras and Phosphatidylserine on the Cell Membrane Studied with Multicolor Super Resolution Microscopy

Cited by 8 publications

References 59 publications

RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling

RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling

Location, location, location: Protein kinase nanoclustering for optimised signalling output

Hydrolysis of Phospholipids in Presence of Phospholipase D:Thrmodynamic and Kinetic Studies of Hydrolysis in Water and Alcoholic Environments

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