Cholesterol depletion induces large scale domain segregation in living cell membranes.

Abstract:

:Local inhomogeneities in lipid composition play a crucial role in regulation of signal transduction and membrane traffic. Nevertheless, most evidence for microdomains in cells remains indirect, and the nature of membrane inhomogeneities has been difficult to characterize. We used lipid analogs and lipid-anchored proteins with varying fluidity preferences to examine the effect of modulating cellular cholesterol on domain formation. We show that lowering cholesterol levels induces formation of visible micrometer-scale domains in the plasma membrane of several mammalian cell types with complementary distributions of fluorescent lipid analogs with preferences for fluid or ordered domains. A uniform distribution is restored by cholesterol repletion. Unexpectedly, cholesterol depletion does not visibly alter the distribution of a crosslinked or uncrosslinked glycosylphosphatidylinositol-anchored protein (the folate receptor). We also examined the effect of varying cholesterol content on the cold Triton X-100 solubility of several membrane constituents. Although a cholesterol analog, dehydroergosterol, and a glycosylphosphatidylinositol-anchored protein are largely retained after extraction, a lipid analog with saturated 16-carbon acyl chains is largely removed when the cellular cholesterol level is lowered. This result indicates that after cholesterol depletion molecules in the more ordered domains can be extracted differentially by cold nonionic detergents.

authors

Hao M,Mukherjee S,Maxfield FR

doi

10.1073/pnas.231377398

keywords:

subject

Has Abstract

pub_date

2001-11-06 00:00:00

pages

13072-7

issue

23

eissn

0027-8424

issn

1091-6490

pii

98/23/13072

journal_volume

98

pub_type

杂志文章
  • Enhanced anticancer activity of nanopreparation containing an MMP2-sensitive PEG-drug conjugate and cell-penetrating moiety.

    abstract::In response to the challenges of cancer chemotherapeutics, including poor physicochemical properties, low tumor targeting, insufficient tumor cell internalization/bioavailability, and side effects, we developed a unique tumor-targeted micellar drug-delivery platform. Using paclitaxel as a model therapeutic, a nanoprep...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1304987110

    authors: Zhu L,Wang T,Perche F,Taigind A,Torchilin VP

    更新日期:2013-10-15 00:00:00

  • Computing trisections of 4-manifolds.

    abstract::We describe an algorithm to compute trisections of orientable four-manifolds using arbitrary triangulations as input. This results in explicit complexity bounds for the trisection genus of a 4-manifold in terms of the number of pentachora (4-simplices) in a triangulation. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1717173115

    authors: Bell M,Hass J,Rubinstein JH,Tillmann S

    更新日期:2018-10-23 00:00:00

  • Design of a membrane transport protein for fluorescence spectroscopy.

    abstract::To modify the lac permease of Escherichia coli for fluorescence spectroscopy, six tryptophan residues at positions 10, 33, 78, 151, 171, and 223 were first replaced individually with phenylalanine by using oligonucleotide-directed site-specific mutagenesis. None of the tryptophan residues is critical for activity, as ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.5.1638

    authors: Menezes ME,Roepe PD,Kaback HR

    更新日期:1990-03-01 00:00:00

  • Identification of tissue-specific cell death using methylation patterns of circulating DNA.

    abstract::Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DN...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1519286113

    authors: Lehmann-Werman R,Neiman D,Zemmour H,Moss J,Magenheim J,Vaknin-Dembinsky A,Rubertsson S,Nellgård B,Blennow K,Zetterberg H,Spalding K,Haller MJ,Wasserfall CH,Schatz DA,Greenbaum CJ,Dorrell C,Grompe M,Zick A,Hubert A,M

    更新日期:2016-03-29 00:00:00

  • Facilitation of murine cardiac L-type Ca(v)1.2 channel is modulated by calmodulin kinase II-dependent phosphorylation of S1512 and S1570.

    abstract::Activity-dependent means of altering calcium (Ca(2)(+)) influx are assumed to be of great physiological consequence, although definitive tests of this assumption have only begun to emerge. Facilitation and inactivation offer two opposing, activity-dependent means of altering Ca(2+) influx via cardiac Ca(v)1.2 calcium ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0914287107

    authors: Blaich A,Welling A,Fischer S,Wegener JW,Köstner K,Hofmann F,Moosmang S

    更新日期:2010-06-01 00:00:00

  • Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody.

    abstract::Inflammatory destruction of insulin-producing beta cells in the pancreatic islets is the hallmark of insulin-dependent diabetes mellitus, a spontaneous autoimmune disease of non-obese diabetic mice resembling human juvenile (type I) diabetes. Histochemical analysis of diabetic pancreata revealed that mononuclear cells...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.1.285

    authors: Weiss L,Slavin S,Reich S,Cohen P,Shuster S,Stern R,Kaganovsky E,Okon E,Rubinstein AM,Naor D

    更新日期:2000-01-04 00:00:00

  • Orthogonal self-assembly of an organoplatinum(II) metallacycle and cucurbit[8]uril that delivers curcumin to cancer cells.

    abstract::Curcumin (Cur) is a naturally occurring anticancer drug isolated from the Curcuma longa plant. It is known to exhibit anticancer properties via inhibiting the STAT3 phosphorylation process. However, its poor water solubility and low bioavailability impede its clinical application. Herein, we used organoplatinum(II) ← ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1803800115

    authors: Datta S,Misra SK,Saha ML,Lahiri N,Louie J,Pan D,Stang PJ

    更新日期:2018-08-07 00:00:00

  • bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans.

    abstract::Very little is known about how animals discriminate pathogens from innocuous microbes. To address this question, we examined infection-response gene induction in the nematode Caenorhabditis elegans. We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0914643107

    authors: Estes KA,Dunbar TL,Powell JR,Ausubel FM,Troemel ER

    更新日期:2010-02-02 00:00:00

  • Comparative oncogenomics identifies breast tumors enriched in functional tumor-initiating cells.

    abstract::The claudin-low subtype is a recently identified rare molecular subtype of human breast cancer that expresses low levels of tight and adherens junction genes and shows high expression of epithelial-to-mesenchymal transition (EMT) genes. These tumors are enriched in gene expression signatures derived from human tumor-i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1018862108

    authors: Herschkowitz JI,Zhao W,Zhang M,Usary J,Murrow G,Edwards D,Knezevic J,Greene SB,Darr D,Troester MA,Hilsenbeck SG,Medina D,Perou CM,Rosen JM

    更新日期:2012-02-21 00:00:00

  • Evolutionary conservation of the insulinoma gene rig and its possible function.

    abstract::We have identified a gene, rig (rat insulinoma gene), that is activated in chemically induced rat insulinomas but not in normal pancreatic islets or in regenerating islets. In the present study, we have found that the insulinoma gene was activated in a BK virus-induced hamster insulinoma cell line and in a spontaneous...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.19.6659

    authors: Inoue C,Shiga K,Takasawa S,Kitagawa M,Yamamoto H,Okamoto H

    更新日期:1987-10-01 00:00:00

  • Insect herbivory, plant defense, and early Cenozoic climate change.

    abstract::Insect damage on fossil leaves from the Central Rocky Mountains, United States, documents the response of herbivores to changing regional climates and vegetation during the late Paleocene (humid, warm temperate to subtropical, predominantly deciduous), early Eocene (humid subtropical, mixed deciduous and evergreen), a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.111069498

    authors: Wilf P,Labandeira CC,Johnson KR,Coley PD,Cutter AD

    更新日期:2001-05-22 00:00:00

  • Decadal predictability without ocean dynamics.

    abstract::This paper shows that the most predictable components of internal variability in coupled atmosphere-ocean models are remarkably similar to the most predictable components of climate models without interactive ocean dynamics (i.e., models whose ocean is represented by a 50-m-deep slab ocean mixed layer with no interact...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1614085114

    authors: Srivastava A,DelSole T

    更新日期:2017-02-28 00:00:00

  • Identification of the 5' end of Rous sarcoma virus RNA.

    abstract::The 5'-terminal triphosphate of the 35S RNA isolated from Rous sarcoma virus is blocked by 7-methylguanosine in 5' linkage with the penultimate nucleoside which is methylated in the 2'-O-ribose position, a type of endgroup found in all animal mRNAs investigated during the past year. The specific nuclease-resistant ter...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.9.3347

    authors: Keith J,Fraenkel-Conrat H

    更新日期:1975-09-01 00:00:00

  • Differential expression of the ToxR regulon in classical and E1 Tor biotypes of Vibrio cholerae is due to biotype-specific control over toxT expression.

    abstract::The two major disease-causing biotypes of Vibrio cholerae, classical and El Tor, exhibit differences in their epidemic nature. Their behavior in the laboratory also differs in that El Tor strains produce two major virulence factors, cholera toxin (CT) and the toxin coregulated pilus (TCP), only under very restricted g...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.15.7991

    authors: DiRita VJ,Neely M,Taylor RK,Bruss PM

    更新日期:1996-07-23 00:00:00

  • Direct evidence for a predominantly exolytic processive mechanism for depolymerization of heparin-like glycosaminoglycans by heparinase I.

    abstract::Heparinase I from Flavobacterium heparinum has important uses for elucidating the complex sequence heterogeneity of heparin-like glycosaminoglycans (HLGAGs). Understanding the biological function of HLGAGs has been impaired by the limited methods for analysis of pure or mixed oligosaccharide fragments. Here, we use me...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.8.4182

    authors: Ernst S,Rhomberg AJ,Biemann K,Sasisekharan R

    更新日期:1998-04-14 00:00:00

  • Motion of a slightly compressible fluid.

    abstract::We show that the motion of a slightly compressible fluid is near that of an incompressible fluid. That is, for a given initial velocity field, the motion of a compressible fluid with large sound speed is near to that of an idealized incompressible fluid. We consider the compressible fluid motion in Lagrangian coordina...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.2.539

    authors: Ebin DG

    更新日期:1975-02-01 00:00:00

  • Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation.

    abstract::Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is a newly recognized condition in children with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These children and adult patients with severe hyperinflammation present with a constellation of symptoms that st...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2010722117

    authors: Cheng MH,Zhang S,Porritt RA,Noval Rivas M,Paschold L,Willscher E,Binder M,Arditi M,Bahar I

    更新日期:2020-10-13 00:00:00

  • Origin of slow spontaneous resting-state neuronal fluctuations in brain networks.

    abstract::Resting- or baseline-state low-frequency (0.01-0.2 Hz) brain activity is observed in fMRI, EEG, and local field potential recordings. These fluctuations were found to be correlated across brain regions and are thought to reflect neuronal activity fluctuations between functionally connected areas of the brain. However,...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1715841115

    authors: Krishnan GP,González OC,Bazhenov M

    更新日期:2018-06-26 00:00:00

  • Mechanism of stimulation of prostaglandin synthesis by a factor from rheumatoid synovial tissue.

    abstract::Rheumatoid synovial cell monolayers, with [1-14C]arachidonic acid ([1-14C]AA) incorporated into cell lipids, are stimulated by a factor (RSF) produced by explant cultures of rheumatoid synovial tissue to produce up to 50-fold increases in [1-14C]prostaglandin E2 and [1-14C]prostaglandin I2. In contrast, levels of free...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.8.5160

    authors: Robinson DR,Bastian D,Hamer PJ,Pichiarallo DM,Stephenson ML

    更新日期:1981-08-01 00:00:00

  • Nucleotides regulate the mechanical hierarchy between subdomains of the nucleotide binding domain of the Hsp70 chaperone DnaK.

    abstract::The regulation of protein function through ligand-induced conformational changes is crucial for many signal transduction processes. The binding of a ligand alters the delicate energy balance within the protein structure, eventually leading to such conformational changes. In this study, we elucidate the energetic and m...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1504625112

    authors: Bauer D,Merz DR,Pelz B,Theisen KE,Yacyshyn G,Mokranjac D,Dima RI,Rief M,Žoldák G

    更新日期:2015-08-18 00:00:00

  • Similar DNA recognition properties of alternatively spliced Drosophila POU factors.

    abstract::The POU-IV or "Brn-3" class of POU-domain transcription factors is represented in Drosophila by I-POU and twin-of-I-POU, alternative splice products of the I-POU gene. I-POU has been previously reported to inhibit DNA binding by the POU-III class factor drifter/Cf1a via the formation of heterodimeric complexes. Here w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.26.15097

    authors: Turner EE

    更新日期:1996-12-24 00:00:00

  • Duplex DNA catalyzes the chemical rearrangement of a malondialdehyde deoxyguanosine adduct.

    abstract::The primary DNA lesion induced by malondialdehyde, a byproduct of lipid peroxidation and prostaglandin synthesis, is 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-pyrimido[1, 2-a]purin-10(3H)-one (M1G). When placed opposite cytosine (underlined) at neutral pH in either the d(GGTMTCCG).d(CGGACACC) or d(ATCGCMCGGCATG). d(C...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.12.6615

    authors: Mao H,Schnetz-Boutaud NC,Weisenseel JP,Marnett LJ,Stone MP

    更新日期:1999-06-08 00:00:00

  • Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool.

    abstract::In mice, recent thymic emigrants (RTEs) make up a large part of the naïve T cell pool and have been suggested to be a distinct short-lived pool. In humans, however, the life span and number of RTEs are unknown. Although (2)H(2)O labeling in young mice showed high thymic-dependent daily naïve T cell production, long te...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0709713105

    authors: Vrisekoop N,den Braber I,de Boer AB,Ruiter AF,Ackermans MT,van der Crabben SN,Schrijver EH,Spierenburg G,Sauerwein HP,Hazenberg MD,de Boer RJ,Miedema F,Borghans JA,Tesselaar K

    更新日期:2008-04-22 00:00:00

  • Inhibition of granulocyte differentiation by G1 cyclins D2 and D3 but not D1.

    abstract::Growth factor-induced signals govern the expression of three D-type cyclins, which, in turn, function as regulatory subunits of cyclin-dependent kinases (cdks) to control cell cycle transitions during the late G1 interval. 32D myeloid cells, which self-renew as uncommitted precursors in interleukin 3 (IL-3), express c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.24.11513

    authors: Kato JY,Sherr CJ

    更新日期:1993-12-15 00:00:00

  • Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice.

    abstract::The activated human Ha-ras oncogene was subjected to the control of the promoter region of the murine whey acidic protein (Wap) gene, which is expressed in mammary epithelial cells in response to lactogenic hormones. The Wap-ras gene was stably introduced into the mouse germ line of five transgenic mice (one male and ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.5.1299

    authors: Andres AC,Schönenberger CA,Groner B,Hennighausen L,LeMeur M,Gerlinger P

    更新日期:1987-03-01 00:00:00

  • Macrophage membrane potential changes associated with gamma 2b/gamma 1 Fc receptor-ligand binding.

    abstract::We have studied the effects of specific ligands of the receptor for the IgG Fc fragment (FcR) on the membrane potential (delta psi) of the macrophage cell line J774 by the [3H]tetraphenylphosphonium ion equilibration technique. We observe a membrane depolarization with binding of FcR ligands that is dependent on the d...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.5.1357

    authors: Young JD,Unkeless JC,Kaback HR,Cohn ZA

    更新日期:1983-03-01 00:00:00

  • Evolutionary dynamics of olfactory receptor genes in Drosophila species.

    abstract::Olfactory receptor (OR) genes are of vital importance for animals to find food, identify mates, and avoid dangers. In mammals, the number of OR genes is large and varies extensively among different orders, whereas, in insects, the extent of interspecific variation appears to be small, although only a few species have ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0702133104

    authors: Nozawa M,Nei M

    更新日期:2007-04-24 00:00:00

  • Tissue-engineered endothelial and epithelial implants differentially and synergistically regulate airway repair.

    abstract::The trilaminate vascular architecture provides biochemical regulation and mechanical integrity. Yet regulatory control can be regained after injury without recapitulating tertiary structure. Tissue-engineered (TE) endothelium controls repair even when placed in the perivascular space of injured vessels. It remains unc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0802463105

    authors: Zani BG,Kojima K,Vacanti CA,Edelman ER

    更新日期:2008-05-13 00:00:00

  • Independent role for presynaptic FMRP revealed by an FMR1 missense mutation associated with intellectual disability and seizures.

    abstract::Fragile X syndrome (FXS) results in intellectual disability (ID) most often caused by silencing of the fragile X mental retardation 1 (FMR1) gene. The resulting absence of fragile X mental retardation protein 1 (FMRP) leads to both pre- and postsynaptic defects, yet whether the pre- and postsynaptic functions of FMRP ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1423094112

    authors: Myrick LK,Deng PY,Hashimoto H,Oh YM,Cho Y,Poidevin MJ,Suhl JA,Visootsak J,Cavalli V,Jin P,Cheng X,Warren ST,Klyachko VA

    更新日期:2015-01-27 00:00:00

  • Arabidopsis cryptochrome 2 (CRY2) functions by the photoactivation mechanism distinct from the tryptophan (trp) triad-dependent photoreduction.

    abstract::Cryptochromes are blue-light receptors mediating various light responses in plants and animals. The photochemical mechanism of cryptochromes is not well understood. It has been proposed that photoactivation of cryptochromes involves the blue-light-dependent photoreduction of flavin adenine dinucleotide via the electro...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1114579108

    authors: Li X,Wang Q,Yu X,Liu H,Yang H,Zhao C,Liu X,Tan C,Klejnot J,Zhong D,Lin C

    更新日期:2011-12-20 00:00:00