Abstract:
:Mechanical force is a determinant of Notch signalling but the mechanism of force detection and its coupling to Notch are unclear. We propose a role for Piezo1 channels, which are mechanically-activated non-selective cation channels. In cultured microvascular endothelial cells, Piezo1 channel activation by either shear stress or a chemical agonist Yoda1 activated a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), a Ca2+-regulated transmembrane sheddase that mediates S2 Notch1 cleavage. Consistent with this observation, we found Piezo1-dependent increase in the abundance of Notch1 intracellular domain (NICD) that depended on ADAM10 and the downstream S3 cleavage enzyme, γ-secretase. Conditional endothelial-specific disruption of Piezo1 in adult mice suppressed the expression of multiple Notch1 target genes in hepatic vasculature, suggesting constitutive functional importance in vivo. The data suggest that Piezo1 is a mechanism conferring force sensitivity on ADAM10 and Notch1 with downstream consequences for sustained activation of Notch1 target genes and potentially other processes.
journal_name
Elifejournal_title
eLifeauthors
Caolo V,Debant M,Endesh N,Futers TS,Lichtenstein L,Bartoli F,Parsonage G,Jones EA,Beech DJdoi
10.7554/eLife.50684subject
Has Abstractpub_date
2020-06-02 00:00:00issn
2050-084Xpii
50684journal_volume
9pub_type
杂志文章相关文献
eLife文献大全abstract::Many marine animals, ranging from corals to fishes, synchronise reproduction to lunar cycles. In the annelid Platynereis dumerilii, this timing is orchestrated by an endogenous monthly (circalunar) clock entrained by moonlight. Whereas daily (circadian) clocks cause extensive transcriptomic and proteomic changes, the ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.41556
更新日期:2019-02-15 00:00:00
abstract::Sequences of events are ubiquitous in sensory, motor, and cognitive function. Key computational operations, including pattern recognition, event prediction, and plasticity, involve neural discrimination of spatio-temporal sequences. Here, we show that synaptically-driven reaction-diffusion pathways on dendrites can pe...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.25827
更新日期:2017-04-19 00:00:00
abstract::Although the elongating ribosome is an efficient helicase, certain mRNA stem-loop structures are known to impede ribosome movement along mRNA and stimulate programmed ribosome frameshifting via mechanisms that are not well understood. Using biochemical and single-molecule Förster resonance energy transfer (smFRET) exp...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.55799
更新日期:2020-05-19 00:00:00
abstract::Dietary restriction increases the longevity of many organisms, but the cell signaling and organellar mechanisms underlying this capability are unclear. We demonstrate that to permit long-term survival in response to sudden glucose depletion, yeast cells activate lipid-droplet (LD) consumption through micro-lipophagy (...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.21690
更新日期:2017-04-10 00:00:00
abstract::Holliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 Å resolution. The GEN1 core is ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.12256
更新日期:2015-12-18 00:00:00
abstract::Sensory navigation results from coordinated transitions between distinct behavioral programs. During chemotaxis in the Drosophila melanogaster larva, the detection of positive odor gradients extends runs while negative gradients promote stops and turns. This algorithm represents a foundation for the control of sensory...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.38740
更新日期:2018-11-22 00:00:00
abstract::WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4+ T cells. Wnk1 is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for the transitio...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56934
更新日期:2020-10-14 00:00:00
abstract::Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, c...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.31515
更新日期:2018-02-05 00:00:00
abstract::The dendritic cell receptor Clec9A facilitates processing of dead cell-derived antigens for cross-presentation and the induction of effective CD8+ T cell immune responses. Here, we show that this process is regulated by E3 ubiquitin ligase RNF41 and define a new ubiquitin-mediated mechanism for regulation of Clec9A, r...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.63452
更新日期:2020-12-02 00:00:00
abstract::The Fluc family of F(-) ion channels protects prokaryotes and lower eukaryotes from the toxicity of environmental F(-). In bacteria, these channels are built as dual-topology dimers whereby the two subunits assemble in antiparallel transmembrane orientation. Recent crystal structures suggested that Fluc channels conta...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.18767
更新日期:2016-07-23 00:00:00
abstract::Synaptic positions underlie precise circuit connectivity. Synaptic positions can be established during embryogenesis and sustained during growth. The mechanisms that sustain synaptic specificity during allometric growth are largely unknown. We performed forward genetic screens in C. elegans for regulators of this proc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.55890
更新日期:2020-04-07 00:00:00
abstract::Translation is a core cellular process carried out by a highly conserved macromolecular machine, the ribosome. There has been remarkable evolutionary adaptation of this machine through the addition of eukaryote-specific ribosomal proteins whose individual effects on ribosome function are largely unknown. Here we show ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.11154
更新日期:2016-04-27 00:00:00
abstract::Peroxiredoxins are H2O2 scavenging enzymes that also carry out H2O2 signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H2O2 and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions not by scavengi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.60346
更新日期:2020-07-14 00:00:00
abstract::Bone destruction relies on interactions between bone and immune cells. Bone-resorbing osteoclasts (OCLs) were recently identified as innate immune cells activating T cells toward tolerance or inflammation. Thus, pathological bone destruction not only relies on increased osteoclast differentiation, but also on the pres...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.54493
更新日期:2020-05-13 00:00:00
abstract::β-Propellers arise through the amplification of a supersecondary structure element called a blade. This process produces toroids of between four and twelve repeats, which are almost always arranged sequentially in a single polypeptide chain. We found that new propellers evolve continuously by amplification from single...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.49853
更新日期:2019-10-15 00:00:00
abstract::How are decisions made between different goods? One theory spanning several fields of neuroscience proposes that their values are distilled to a single common neural currency, the calculation of which allows for rational decisions. The orbitofrontal cortex (OFC) is thought to play a critical role in this process, base...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.38963
更新日期:2018-10-03 00:00:00
abstract::Cells use molecular circuits to interpret and respond to extracellular cues, such as hormones and cytokines, which are often released in a temporally varying fashion. In this study, we combine microfluidics, time-lapse microscopy, and computational modeling to investigate how the type I interferon (IFN)-responsive reg...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.58825
更新日期:2020-09-18 00:00:00
abstract::Comprehensively elucidating the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) latency is a priority to achieve a functional cure. As current 'shock' agents failed to efficiently reactivate the latent reservoir, it is important to discover new targets for developing more efficient latency-reversin...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.42426
更新日期:2019-01-17 00:00:00
abstract::Oncogenic human papillomaviruses (HPV) are small DNA viruses that infect keratinocytes. After HPV binding to cell surface receptors, a cascade of molecular interactions mediates the infectious cellular internalization of virus particles. Aside from the virus itself, important molecular players involved in virus entry ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44345
更新日期:2019-05-20 00:00:00
abstract::Contrary to dogma, evolutionarily young and dynamic genes can encode essential functions. We find that evolutionarily dynamic ZAD-ZNF genes, which encode the most abundant class of insect transcription factors, are more likely to encode essential functions in Drosophila melanogaster than ancient, conserved ZAD-ZNF gen...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.63368
更新日期:2020-11-10 00:00:00
abstract::Genetic techniques have shed new light on the organization of the neurons in the ventral nervous system of the fruit fly. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.10317
更新日期:2015-08-28 00:00:00
abstract::Rod and cone photoreceptors are highly similar in many respects but they have important functional and molecular differences. Here, we investigate genome-wide patterns of DNA methylation and chromatin accessibility in mouse rods and cones and correlate differences in these features with gene expression, histone marks,...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.11613
更新日期:2016-03-07 00:00:00
abstract::Negative feedback regulation, that is the ability of a gene to repress its own synthesis, is the most abundant regulatory motif known to biology. Frequently reported for transcriptional regulators, negative feedback control relies on binding of a transcription factor to its own promoter. Here, we report a novel mechan...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.58836
更新日期:2020-08-03 00:00:00
abstract::Post-transcriptional control by small regulatory RNA (sRNA) is critical for rapid adaptive processes. sRNAs can directly modulate mRNA degradation in Proteobacteria without interfering with translation. However, Firmicutes have a fundamentally different set of ribonucleases for mRNA degradation and whether sRNAs can r...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.23602
更新日期:2017-04-24 00:00:00
abstract::New ages for flowstone, sediments and fossil bones from the Dinaledi Chamber are presented. We combined optically stimulated luminescence dating of sediments with U-Th and palaeomagnetic analyses of flowstones to establish that all sediments containing Homo naledi fossils can be allocated to a single stratigraphic ent...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.24231
更新日期:2017-05-09 00:00:00
abstract::The growth of preprints in the life sciences has been reported widely and is driving policy changes for journals and funders, but little quantitative information has been published about preprint usage. Here, we report how we collected and analyzed data on all 37,648 preprints uploaded to bioRxiv.org, the largest biol...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45133
更新日期:2019-04-24 00:00:00
abstract::During inflammation, serum amyloid A proteins transport retinol to infected tissues. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.04246
更新日期:2014-09-02 00:00:00
abstract::Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.15258
更新日期:2016-06-22 00:00:00
abstract::Recent work draws attention to community-community encounters ('coalescence') as likely an important factor shaping natural ecosystems. This work builds on MacArthur's classic model of competitive coexistence to investigate such community-level competition in a minimal theoretical setting. It is shown that the ability...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.15747
更新日期:2016-06-16 00:00:00
abstract::The TP53 tumor-suppressor gene is mutated in >50% of human tumors and Li-Fraumeni patients with germ line inactivation are predisposed to developing cancer. Here, we generated tp53 deleted zebrafish that spontaneously develop malignant peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an aggressive ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.37202
更新日期:2018-09-07 00:00:00