Functional impact of cholesterol sequestration on actin cytoskeleton in normal and transformed fibroblasts

Chubinskiy-Nadezhdin, V. I.; Ефремова, Т. В.; Khaitlina, Sofia; Morachevskaya, E. A.

doi:10.1002/cbin.10079

Cited by 26 publications

(22 citation statements)

References 30 publications

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“…Recent reports that cholesterol depletion perturbs cytoskeletal organization (Ramprasad et al, 2007; Sun et al, 2007; Qi et al, 2009; Norman et al, 2010; Chubinskiy-Nadezhdin et al, 2013; Dick et al, 2013) may suggest that cholesterol depletion inhibits antigen patching by preventing the cytoskeletal proteins from actively clustering the crosslinked antigens. But, as mentioned above, if the cytoskeleton, and not lipid rafts, mediates the clustering of crosslinked antigens, the finding that crosslinking induces glycosphingolipid capping implies the glycosphingolipids in the outer leaflet of the plasma membrane are indirectly associated with cytoskeletal proteins.…”

Section: Glycosphingolipid Redistribution Induced By Antigen Crosslinmentioning

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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Section: Glycosphingolipid Redistribution Induced By Antigen Crosslinmentioning

confidence: 99%

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

Kraft

2017

Front. Cell Dev. Biol.

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“…Interestingly, recent in vivo experiments have shown that actin filaments that are attached to the membrane induce the formation of liquid-ordered domains1415. Conversely, cholesterol sequestration alters the ratio between liquid-ordered (raft-like) and liquid-disordered lipid phases, causing dramatic changes in the dynamics of the actin cytoskeleton16. All this evidence suggests a dynamic interplay between the actin cytoskeleton and the lipid membrane that alters the normal diffusion of proteins in the membrane17.…”

mentioning

confidence: 99%

Interplay of cytoskeletal activity and lipid phase stability in dynamic protein recruitment and clustering

Gómez-Llobregat

Buceta²,

Reigada

2013

Sci Rep

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Recent experiments have revealed that some membrane proteins aggregate to form clusters. This type of process has been proven to be dynamic and to be actively maintained by external kinetics. Additionally, this dynamic recruiting is cholesterol- and actin-dependent, suggesting that raft organization and cytoskeleton rearrangement play a crucial role. In the present study, we propose a simple model that provides a general framework to describe the dynamical behavior of lipid-protein assemblies. Our results suggest that lipid-mediated interactions and cytoskeleton-anchored proteins contribute to the modulation of such behavior. In particular, we find a resonant condition between the membrane protein and cytoskeleton dynamics that results in the invariance of the ratio of clustered proteins that is found in in vivo experimental observations.

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“…Therefore membrane CHO and not SM was critical for TSH-TSHR interaction. Depletion of membrane CHO by methyl-beta-cyclodextrin resulted in a disruption of lipid rafts in plasma membrane [26] whereas extensive sphingolipid depletion did not affect lipid raft integrity [27]. Rapid changes of the cytoskeleton as reaction to gravitational changes were reported in diverse cell types [28], [29] and they could be responsible for changes in surface receptors [1].…”

Section: Discussionmentioning

confidence: 99%

A Firmer Understanding of the Effect of Hypergravity on Thyroid Tissue: Cholesterol and Thyrotropin Receptor

et al. 2014

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Maintaining a good health requires the maintenance of a body homeostasis which largely depends on correct functioning of thyroid gland. The cells of the thyroid tissue are strongly sensitive to hypogravity, as already proven in mice after returning to the earth from long-term space missions. Here we studied whether hypergravity may be used to counteract the physiological deconditioning of long-duration spaceflight. We investigated the influence of hypergravity on key lipids and proteins involved in thyroid tissue function. We quantified cholesterol (CHO) and different species of sphingomyelin (SM) and ceramide, analysed thyrotropin (TSH) related molecules such as thyrotropin-receptor (TSHR), cAMP, Caveolin-1 and molecule signalling such as Signal transducer and activator of transcription-3 (STAT3). The hypergravity treatment resulted in the upregulation of the TSHR and Caveolin-1 and downregulation of STAT3 without changes of cAMP. TSHR lost its specific localization and spread throughout the cell membrane; TSH treatment facilitated the shedding of α subunit of TSHR and its releasing into the extracellular space. No specific variations were observed for each species of SM and ceramide. Importantly, the level of CHO was strongly reduced. In conclusion, hypergravity conditions induce change in CHO and TSHR of thyroid gland. The possibility that lipid rafts are strongly perturbed by hypergravity-induced CHO depletion by influencing TSH-TSHR interaction was discussed.

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Functional impact of cholesterol sequestration on actin cytoskeleton in normal and transformed fibroblasts

Cited by 26 publications

References 30 publications

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

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

Interplay of cytoskeletal activity and lipid phase stability in dynamic protein recruitment and clustering

A Firmer Understanding of the Effect of Hypergravity on Thyroid Tissue: Cholesterol and Thyrotropin Receptor

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