Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export.

Abstract:

:LAMP1 and LAMP2 proteins are highly abundant, ubiquitous, mammalian proteins that line the lysosome limiting membrane, and protect it from lysosomal hydrolase action. LAMP2 deficiency causes Danon's disease, an X-linked hypertrophic cardiomyopathy. LAMP2 is needed for chaperone-mediated autophagy, and its expression improves tissue function in models of aging. We show here that human LAMP1 and LAMP2 bind cholesterol in a manner that buries the cholesterol 3β-hydroxyl group; they also bind tightly to NPC1 and NPC2 proteins that export cholesterol from lysosomes. Quantitation of cellular LAMP2 and NPC1 protein levels suggest that LAMP proteins represent a significant cholesterol binding site at the lysosome limiting membrane, and may signal cholesterol availability. Functional rescue experiments show that the ability of human LAMP2 to facilitate cholesterol export from lysosomes relies on its ability to bind cholesterol directly.

journal_name

Elife

journal_title

eLife

authors

Li J,Pfeffer SR

doi

10.7554/eLife.21635

subject

Has Abstract

pub_date

2016-09-24 00:00:00

issn

2050-084X

journal_volume

5

pub_type

杂志文章

相关文献

eLife文献大全
  • The neuropeptide tachykinin is essential for pheromone detection in a gustatory neural circuit.

    abstract::Gustatory pheromones play an essential role in shaping the behavior of many organisms. However, little is known about the processing of taste pheromones in higher order brain centers. Here, we describe a male-specific gustatory circuit in Drosophila that underlies the detection of the anti-aphrodisiac pheromone (3R,11...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.06914

    authors: Shankar S,Chua JY,Tan KJ,Calvert ME,Weng R,Ng WC,Mori K,Yew JY

    更新日期:2015-06-17 00:00:00

  • Telomeric double-strand DNA-binding proteins DTN-1 and DTN-2 ensure germline immortality in Caenorhabditis elegans.

    abstract::Telomeres are nucleoprotein complexes at the ends of chromosomes and are indispensable for the protection and lengthening of terminal DNA. Despite the evolutionarily conserved roles of telomeres, the telomeric double-strand DNA (dsDNA)-binding proteins have evolved rapidly. Here, we identified double-strand telomeric ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.64104

    authors: Yamamoto I,Zhang K,Zhang J,Vorontsov E,Shibuya H

    更新日期:2021-01-21 00:00:00

  • Structural and functional characterization of G protein-coupled receptors with deep mutational scanning.

    abstract::The >800 human G protein-coupled receptors (GPCRs) are responsible for transducing diverse chemical stimuli to alter cell state- and are the largest class of drug targets. Their myriad structural conformations and various modes of signaling make it challenging to understand their structure and function. Here, we devel...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.54895

    authors: Jones EM,Lubock NB,Venkatakrishnan AJ,Wang J,Tseng AM,Paggi JM,Latorraca NR,Cancilla D,Satyadi M,Davis JE,Babu MM,Dror RO,Kosuri S

    更新日期:2020-10-21 00:00:00

  • Cholinergic modulation of hippocampal calcium activity across the sleep-wake cycle.

    abstract::Calcium is a critical second messenger in neurons that contributes to learning and memory, but how the coordination of action potentials of neuronal ensembles with the hippocampal local field potential (LFP) is reflected in dynamic calcium activity remains unclear. Here, we recorded hippocampal calcium activity with e...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.39777

    authors: Zhou H,Neville KR,Goldstein N,Kabu S,Kausar N,Ye R,Nguyen TT,Gelwan N,Hyman BT,Gomperts SN

    更新日期:2019-03-07 00:00:00

  • Rat behavior and dopamine release are modulated by conspecific distress.

    abstract::Rats exhibit 'empathy' making them a model to understand the neural underpinnings of such behavior. We show data consistent with these findings, but also that behavior and dopamine (DA) release reflects subjective rather than objective evaluation of appetitive and aversive events that occur to another. We recorded DA ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.38090

    authors: Lichtenberg NT,Lee B,Kashtelyan V,Chappa BS,Girma HT,Green EA,Kantor S,Lagowala DA,Myers MA,Potemri D,Pecukonis MG,Tesfay RT,Walters MS,Zhao AC,Blair RJR,Cheer JF,Roesch MR

    更新日期:2018-11-28 00:00:00

  • G protein βγ subunits inhibit TRPM3 ion channels in sensory neurons.

    abstract::Transient receptor potential (TRP) ion channels in peripheral sensory neurons are functionally regulated by hydrolysis of the phosphoinositide PI(4,5)P2 and changes in the level of protein kinase mediated phosphorylation following activation of various G protein coupled receptors. We now show that the activity of TRPM...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.26138

    authors: Quallo T,Alkhatib O,Gentry C,Andersson DA,Bevan S

    更新日期:2017-08-15 00:00:00

  • Structural basis of TRPC4 regulation by calmodulin and pharmacological agents.

    abstract::Canonical transient receptor potential channels (TRPC) are involved in receptor-operated and/or store-operated Ca2+ signaling. Inhibition of TRPCs by small molecules was shown to be promising in treating renal diseases. In cells, the channels are regulated by calmodulin (CaM). Molecular details of both CaM and drug bi...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.60603

    authors: Vinayagam D,Quentin D,Yu-Strzelczyk J,Sitsel O,Merino F,Stabrin M,Hofnagel O,Yu M,Ledeboer MW,Nagel G,Malojcic G,Raunser S

    更新日期:2020-11-25 00:00:00

  • Pericytes are progenitors for coronary artery smooth muscle.

    abstract::Epicardial cells on the heart's surface give rise to coronary artery smooth muscle cells (caSMCs) located deep in the myocardium. However, the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries. Here, we use clonal analysis and lineage tracing...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.10036

    authors: Volz KS,Jacobs AH,Chen HI,Poduri A,McKay AS,Riordan DP,Kofler N,Kitajewski J,Weissman I,Red-Horse K

    更新日期:2015-10-19 00:00:00

  • The human gut and groundwater harbor non-photosynthetic bacteria belonging to a new candidate phylum sibling to Cyanobacteria.

    abstract::Cyanobacteria were responsible for the oxygenation of the ancient atmosphere; however, the evolution of this phylum is enigmatic, as relatives have not been characterized. Here we use whole genome reconstruction of human fecal and subsurface aquifer metagenomic samples to obtain complete genomes for members of a new c...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.01102

    authors: Di Rienzi SC,Sharon I,Wrighton KC,Koren O,Hug LA,Thomas BC,Goodrich JK,Bell JT,Spector TD,Banfield JF,Ley RE

    更新日期:2013-10-01 00:00:00

  • The transcriptional response to tumorigenic polarity loss in Drosophila.

    abstract::Loss of polarity correlates with progression of epithelial cancers, but how plasma membrane misorganization drives oncogenic transcriptional events remains unclear. The polarity regulators of the Drosophila Scribble (Scrib) module are potent tumor suppressors and provide a model for mechanistic investigation. RNA prof...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.03189

    authors: Bunker BD,Nellimoottil TT,Boileau RM,Classen AK,Bilder D

    更新日期:2015-02-26 00:00:00

  • Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery.

    abstract::Altered insulin signaling has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathy and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on neuronal function is incomplete. Here, we show that cell aut...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.16807

    authors: Mahoney RE,Azpurua J,Eaton BA

    更新日期:2016-08-15 00:00:00

  • Monosynaptic tracing maps brain-wide afferent oligodendrocyte precursor cell connectivity.

    abstract::Neurons form bona fide synapses with oligodendrocyte precursor cells (OPCs), but the circuit context of these neuron to OPC synapses remains incompletely understood. Using monosynaptically-restricted rabies virus tracing of OPC afferents, we identified extensive afferent synaptic inputs to OPCs residing in secondary m...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.49291

    authors: Mount CW,Yalçın B,Cunliffe-Koehler K,Sundaresh S,Monje M

    更新日期:2019-10-18 00:00:00

  • Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation.

    abstract::Transposable elements (TEs), the movement of which can damage the genome, are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in the sperm companion cell - vegetative cell (VC) - of the flowering plant Arabidopsis thaliana. However, the extent and mechanism of this activation are unknown. Here w...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.42530

    authors: He S,Vickers M,Zhang J,Feng X

    更新日期:2019-05-28 00:00:00

  • Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication.

    abstract::To initiate DNA replication, cells first load an MCM helicase double hexamer at origins in a reaction requiring ORC, Cdc6, and Cdt1, also called pre-replicative complex (pre-RC) assembly. The essential mechanistic role of Cdc6 ATP hydrolysis in this reaction is still incompletely understood. Here, we show that althoug...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.05795

    authors: Chang F,Riera A,Evrin C,Sun J,Li H,Speck C,Weinreich M

    更新日期:2015-08-25 00:00:00

  • Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci.

    abstract::Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.02557

    authors: Noordermeer D,Leleu M,Schorderet P,Joye E,Chabaud F,Duboule D

    更新日期:2014-04-29 00:00:00

  • A liquid-like organelle at the root of motile ciliopathy.

    abstract::Motile ciliopathies are characterized by specific defects in cilia beating that result in chronic airway disease, subfertility, ectopic pregnancy, and hydrocephalus. While many patients harbor mutations in the dynein motors that drive cilia beating, the disease also results from mutations in so-called dynein axonemal ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.38497

    authors: Huizar RL,Lee C,Boulgakov AA,Horani A,Tu F,Marcotte EM,Brody SL,Wallingford JB

    更新日期:2018-12-18 00:00:00

  • Transmission genetics of drug-resistant hepatitis C virus.

    abstract::Antiviral development is plagued by drug resistance and genetic barriers to resistance are needed. For HIV and hepatitis C virus (HCV), combination therapy has proved life-saving. The targets of direct-acting antivirals for HCV infection are NS3/4A protease, NS5A phosphoprotein and NS5B polymerase. Differential visual...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.32579

    authors: van Buuren N,Tellinghuisen TL,Richardson CD,Kirkegaard K

    更新日期:2018-03-28 00:00:00

  • Loss of centromere function drives karyotype evolution in closely related Malassezia species.

    abstract::Genomic rearrangements associated with speciation often result in variation in chromosome number among closely related species. Malassezia species show variable karyotypes ranging between six and nine chromosomes. Here, we experimentally identified all eight centromeres in M. sympodialis as 3-5-kb long kinetochore-bou...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.53944

    authors: Sankaranarayanan SR,Ianiri G,Coelho MA,Reza MH,Thimmappa BC,Ganguly P,Vadnala RN,Sun S,Siddharthan R,Tellgren-Roth C,Dawson TL Jnr,Heitman J,Sanyal K

    更新日期:2020-01-20 00:00:00

  • De-repression of the RAC activator ELMO1 in cancer stem cells drives progression of TGFβ-deficient squamous cell carcinoma from transition zones.

    abstract::Squamous cell carcinomas occurring at transition zones are highly malignant tumors with poor prognosis. The identity of the cell population and the signaling pathways involved in the progression of transition zone squamous cell carcinoma are poorly understood, hence representing limited options for targeted therapies....

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.22914

    authors: McCauley HA,Chevrier V,Birnbaum D,Guasch G

    更新日期:2017-02-21 00:00:00

  • Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement.

    abstract::Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility. The Saccharomyces cerevisiae RSC (Remodeling the Structure of Chromatin) complex, a member of the SWI/SNF chromatin remodeler family, plays critical roles in genome maintenance, tra...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.54449

    authors: Patel AB,Moore CM,Greber BJ,Luo J,Zukin SA,Ranish J,Nogales E

    更新日期:2019-12-30 00:00:00

  • Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats.

    abstract::After paralyzing spinal cord injury the adult nervous system has little ability to 'heal' spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weig...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.23532

    authors: Manohar A,Foffani G,Ganzer PD,Bethea JR,Moxon KA

    更新日期:2017-06-29 00:00:00

  • Spatial sequestration and detoxification of Huntingtin by the ribosome quality control complex.

    abstract::Huntington disease (HD) is a neurological disorder caused by polyglutamine expansions in mutated Huntingtin (mHtt) proteins, rendering them prone to form inclusion bodies (IB). We report that in yeast, such IB formation is a factor-dependent process subjected to age-related decline. A genome-wide, high-content imaging...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.11792

    authors: Yang J,Hao X,Cao X,Liu B,Nyström T

    更新日期:2016-04-01 00:00:00

  • Near-infrared photoactivatable control of Ca(2+) signaling and optogenetic immunomodulation.

    abstract::The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed 'Opto-CRAC') that selectively ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.10024

    authors: He L,Zhang Y,Ma G,Tan P,Li Z,Zang S,Wu X,Jing J,Fang S,Zhou L,Wang Y,Huang Y,Hogan PG,Han G,Zhou Y

    更新日期:2015-12-08 00:00:00

  • Targeting the link between late pregnancy and breast cancer.

    abstract::Why does a first pregnancy after age 35 increase the risk of breast cancer, and what can be done to combat this? ...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.01926

    authors: Chakravarthi BV,Varambally S

    更新日期:2013-12-31 00:00:00

  • Genetically tunable frustration controls allostery in an intrinsically disordered transcription factor.

    abstract::Intrinsically disordered proteins (IDPs) present a functional paradox because they lack stable tertiary structure, but nonetheless play a central role in signaling, utilizing a process known as allostery. Historically, allostery in structured proteins has been interpreted in terms of propagated structural changes that...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.30688

    authors: Li J,White JT,Saavedra H,Wrabl JO,Motlagh HN,Liu K,Sowers J,Schroer TA,Thompson EB,Hilser VJ

    更新日期:2017-10-12 00:00:00

  • Control of endothelial cell polarity and sprouting angiogenesis by non-centrosomal microtubules.

    abstract::Microtubules control different aspects of cell polarization. In cells with a radial microtubule system, a pivotal role in setting up asymmetry is attributed to the relative positioning of the centrosome and the nucleus. Here, we show that centrosome loss had no effect on the ability of endothelial cells to polarize an...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.33864

    authors: Martin M,Veloso A,Wu J,Katrukha EA,Akhmanova A

    更新日期:2018-03-16 00:00:00

  • Establishment and stability of the latent HIV-1 DNA reservoir.

    abstract::HIV-1 infection cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). In a previous paper (Zanini et al, 2015) we documented HIV-1 evolution in 10 untreated patients. Here we characterize establishment, turnover, and evoluti...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.18889

    authors: Brodin J,Zanini F,Thebo L,Lanz C,Bratt G,Neher RA,Albert J

    更新日期:2016-11-15 00:00:00

  • Lipids and ions traverse the membrane by the same physical pathway in the nhTMEM16 scramblase.

    abstract::From bacteria to mammals, different phospholipid species are segregated between the inner and outer leaflets of the plasma membrane by ATP-dependent lipid transporters. Disruption of this asymmetry by ATP-independent phospholipid scrambling is important in cellular signaling, but its mechanism remains incompletely und...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.28671

    authors: Jiang T,Yu K,Hartzell HC,Tajkhorshid E

    更新日期:2017-09-16 00:00:00

  • High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila.

    abstract::Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.22617

    authors: Zhu JY,Fu Y,Nettleton M,Richman A,Han Z

    更新日期:2017-01-20 00:00:00

  • Centering and symmetry breaking in confined contracting actomyosin networks.

    abstract::Centering and decentering of cellular components is essential for internal organization of cells and their ability to perform basic cellular functions such as division and motility. How cells achieve proper localization of their organelles is still not well-understood, especially in large cells such as oocytes. Here, ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.55368

    authors: Ierushalmi N,Malik-Garbi M,Manhart A,Abu Shah E,Goode BL,Mogilner A,Keren K

    更新日期:2020-04-21 00:00:00