Abstract：
:Lipoprotein cholesterol is delivered to the limiting membrane of late endosomes/lysosomes (LELs) by Niemann-Pick C1 (NPC1). However, the mechanism of cholesterol transport from LELs to the endoplasmic reticulum (ER) is poorly characterized. We report that oxysterol-binding protein-related protein 1L (ORP1L) is necessary for this stage of cholesterol export. CRISPR-mediated knockout of ORP1L in HeLa and HEK293 cells reduced esterification of cholesterol to the level in NPC1 knockout cells, and it increased the expression of sterol-regulated genes and de novo cholesterol synthesis, indicative of a block in cholesterol transport to the ER. In the absence of this transport pathway, cholesterol-enriched LELs accumulated in the Golgi/perinuclear region. Cholesterol delivery to the ER required the sterol-, phosphatidylinositol 4-phosphate-, and vesicle-associated membrane protein-associated protein (VAP)-binding activities of ORP1L, as well as NPC1 expression. These results suggest that ORP1L-dependent membrane contacts between LELs and the ER coordinate cholesterol transfer with the retrograde movement of endo-lysosomal vesicles.
journal_name
Cell Repjournal_title
Cell reportsauthors
Zhao K,Ridgway NDdoi
10.1016/j.celrep.2017.05.028subject
Has Abstractpub_date
2017-05-30 00:00:00pages
1807-1818issue
9issn
2211-1247pii
S2211-1247(17)30653-8journal_volume
19pub_type
杂志文章相关文献
Cell Reports文献大全abstract：:As three-dimensional cell culture formats gain in popularity, there emerges a need for tools that produce vast amounts of data on individual cells within the spheroids or organoids. Here, we present a microfluidic platform that provides access to such data by parallelizing the manipulation of individual spheroids with...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107670
更新日期：2020-05-26 00:00:00
abstract：:Effector, but not naïve, T cells are activated by toll-like receptor-2 (TLR2) stimulation, leading to cytokine production and proliferation. We found that the differential response is attributable to the lack of expression of the adaptor protein TIRAP in naive T cells. TIRAP expression is induced upon T-cell receptor ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107911
更新日期：2020-07-21 00:00:00
abstract：:The macrophage NLRC4 inflammasome drives potent innate immune responses against Salmonella by eliciting caspase-1-dependent proinflammatory cytokine production (e.g., interleukin-1β [IL-1β]) and pyroptotic cell death. However, the potential contribution of other cell types to inflammasome-mediated host defense against...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.06.028
更新日期：2014-07-24 00:00:00
abstract：:Insulin stimulates glucose uptake through the membrane translocation of GLUT4 and GLUT1. Peroxisome proliferator-activated receptor γ (PPARγ) enhances insulin sensitivity. Here, we demonstrate that insulin stimulates GLUT4 and GLUT1 translocation, and glucose uptake, by activating the signaling pathway involving nicot...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2012.10.018
更新日期：2012-12-27 00:00:00
abstract：:The histone methyl transferase enhancer of zeste homolog 2 (EZH2) is a master transcriptional regulator involved in histone H3 lysine 27 trimethylation. We aimed to elucidate the precise post-translational regulations of EZH2 and their role in cancer pathogenesis. Here, we show that SET and MYND domain containing 2 (S...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.10.004
更新日期：2019-11-05 00:00:00
abstract：:Transcription of developmental genes is controlled by multiple enhancers. Frequently, more than one enhancer can activate transcription from the same promoter in the same cells. How is regulatory information from multiple enhancers combined to determine the overall expression output? We measure nascent transcription d...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.01.115
更新日期：2019-02-26 00:00:00
abstract：:Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocap...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108666
更新日期：2021-01-26 00:00:00
abstract：:The twin-ATPase ABCE1 has a vital function in mRNA translation by recycling terminated or stalled ribosomes. As for other functionally distinct ATP-binding cassette (ABC) proteins, the mechanochemical coupling of ATP hydrolysis to conformational changes remains elusive. Here, we use an integrated biophysical approach ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.06.052
更新日期：2019-07-16 00:00:00
abstract：:Glioblastoma (GBM) is highly refractory to therapy and associated with poor clinical outcome. Here, we reveal a critical function of the promitotic and adhesion-mediating discoidin domain receptor 1 (DDR1) in modulating GBM therapy resistance. In GBM cultures and clinical samples, we show a DDR1 and GBM stem cell mark...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.02.096
更新日期：2019-03-26 00:00:00
abstract：:Proper control of DNA replication is essential to ensure faithful transmission of genetic material and prevent chromosomal aberrations that can drive cancer progression and developmental disorders. DNA replication is regulated primarily at the level of initiation and is under strict cell-cycle regulation. Importantly,...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.10.005
更新日期：2014-11-06 00:00:00
abstract：:Obesity is associated with colon cancer pathogenesis, but the underlying mechanism is actively debated. Here, we confirm that diet-induced obesity promotes tumor growth in two murine colon cancer models and show that this effect is reversed by an orally administered controlled-release mitochondrial protonophore (CRMP)...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.06.008
更新日期：2018-07-03 00:00:00
abstract：:Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property chan...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.02.022
更新日期：2020-03-03 00:00:00
abstract：:Cockayne syndrome (CS) is a severe neurodevelopmental disorder characterized by growth abnormalities, premature aging, and photosensitivity. Mutation of Cockayne syndrome B (CSB) affects neuronal gene expression and differentiation, so we attempted to bypass its function by expressing downstream target genes. Intrigui...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.02.051
更新日期：2016-03-22 00:00:00
abstract：:Experience-dependent synapse refinement is essential for functional optimization of neural circuits. However, how sensory experience sculpts excitatory synaptic transmission is poorly understood. Here, we show that despite substantial remodeling of synaptic connectivity, AMPAR-mediated synaptic transmission remains at...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.12.084
更新日期：2017-01-24 00:00:00
abstract：:The NMDA spike is a long-lasting nonlinear phenomenon initiated locally in the dendritic branches of a variety of cortical neurons. It plays a key role in synaptic plasticity and in single-neuron computations. Combining dynamic system theory and computational approaches, we now explore how the timing of synaptic inhib...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.10.035
更新日期：2017-11-07 00:00:00
abstract：:Interest in manipulating the gut microbiota to treat disease has led to a need for understanding how organisms can establish themselves when introduced into a host with an intact microbial community. Here, we employ the concept of orthogonal niche engineering: a resource typically absent from the diet, seaweed, create...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.07.032
更新日期：2018-08-14 00:00:00
abstract：:Stable unannotated transcripts (SUTs), some of which overlap protein-coding genes in antisense direction, are a class of non-coding RNAs. While case studies have reported important regulatory roles for several of such RNAs, their general impact on protein abundance regulation of the overlapping gene is not known. To t...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.05.043
更新日期：2016-06-21 00:00:00
abstract：:Genetic differences between humans and in vivo model systems, including mice and nonhuman primates, make it difficult to predict the efficacy of immunoglobulin G (IgG) activity in humans and understand the molecular and cellular mechanisms underlying that activity. To bridge this gap, we established a small-animal mod...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.02.041
更新日期：2014-04-10 00:00:00
abstract：:Supernumerary centrosomes promote the assembly of abnormal spindles in many human cancers. The observation that modest changes in the centrosomal levels of Mps1 kinase can cause centrosome overduplication in human cells suggests the existence of a regulatory system that may tightly control its centrosomal stability. H...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.10.039
更新日期：2015-11-24 00:00:00
abstract：:Organisms need to assess their nutritional state and adapt their digestive capacity to the demands for various nutrients. Modulation of digestive enzyme production represents a rational step to regulate nutriment uptake. However, the role of digestion in nutrient homeostasis has been largely neglected. In this study, ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.08.064
更新日期：2014-10-09 00:00:00
abstract：:The rate of protein synthesis varies according to the mRNA sequence in ways that affect gene expression. Global analysis of translational pausing is now possible with ribosome profiling. Here, we revisit an earlier report that Shine-Dalgarno sequences are the major determinant of translational pausing in bacteria. Usi...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.12.073
更新日期：2016-02-02 00:00:00
abstract：:Current theories of muscle contraction propose that the power stroke of a myosin motor is the sole source of mechanical energy driving the sliding filaments of a contracting muscle. These models exclude titin, the largest protein in the human body, which determines the passive elasticity of muscles. Here, we show that...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.01.025
更新日期：2016-02-16 00:00:00
abstract：:Interleukin-1 receptor antagonist (IL-1Ra) is elevated in the circulation during obesity and type 2 diabetes (T2D) but is decreased in islets from patients with T2D. The protective role of local IL-1Ra was investigated in pancreatic islet β cell (βIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific IL-1Ra knoc...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.01.063
更新日期：2018-02-13 00:00:00
abstract：:In budding yeast, a mother cell can produce a finite number of daughter cells before it stops dividing and dies. Such entry into senescence is thought to result from a progressive decline in physiological function, including a loss of mitochondrial membrane potential (ΔΨ). Here, we developed a microfluidic device to m...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.11.013
更新日期：2013-12-26 00:00:00
abstract：:Epithelial tissues, such as the skin, rely on cellular plasticity of stem cells (SCs) from different niches to restore tissue function after injury. How these molecularly and functionally diverse SC populations respond to injury remains elusive. Here, we genetically labeled Lgr5- or Lgr6-expressing cells from the hair...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.09.059
更新日期：2018-10-16 00:00:00
abstract：:The flat bones of the skull are densely innervated during development, but little is known regarding their role during repair. We describe a neurotrophic mechanism that directs sensory nerve transit in the mouse calvaria. Patent cranial suture mesenchyme represents an NGF (nerve growth factor)-rich domain, in which se...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107696
更新日期：2020-05-26 00:00:00
abstract：:The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functi...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.02.041
更新日期：2017-03-07 00:00:00
abstract：:The metabolic enzyme phosphoglycerate mutase 1 (PGAM1) is overexpressed in several types of cancer, suggesting an additional function beyond its established role in the glycolytic pathway. We here report that PGAM1 is overexpressed in gliomas where it increases the efficiency of the DNA damage response (DDR) pathway b...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.03.082
更新日期：2020-04-14 00:00:00
abstract：:The number of essential telomerase components in the active ribonucleoprotein (RNP) has important implications for its mechanism of action yet is by and large unknown. We report that two differentially tagged TLC1 RNAs endogenously expressed in a heterozygous diploid and simultaneously detected via multi-color fluores...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.06.045
更新日期：2015-07-21 00:00:00
abstract：:There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl, and cyprodinil with ∼3,600 compounds in diverse fungal species, we generated a deep reservoir of chemical-chemical in...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.10.018
更新日期：2015-11-17 00:00:00
