Abstract:
:Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and α1-adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na+ current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure.
journal_name
Elifejournal_title
eLifeauthors
Bulley S,Fernández-Peña C,Hasan R,Leo MD,Muralidharan P,Mackay CE,Evanson KW,Moreira-Junior L,Mata-Daboin A,Burris SK,Wang Q,Kuruvilla KP,Jaggar JHdoi
10.7554/eLife.42628subject
Has Abstractpub_date
2018-12-04 00:00:00issn
2050-084Xpii
42628journal_volume
7pub_type
杂志文章相关文献
eLife文献大全abstract::The importance of cultural processes to behavioural diversity in our closest living relatives is central to revealing the evolutionary origins of human culture. However, the bonobo is often overlooked as a candidate model. Further, a prominent critique to many examples of proposed animal cultures is premature exclusio...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.59191
更新日期:2020-09-01 00:00:00
abstract::The non-canonical Wnt/Ca2+ signaling pathway plays important roles in embryonic development, tissue formation and diseases. However, it is unclear how the Wnt ligand-stimulated, G protein-coupled receptor Frizzled activates phospholipases for calcium release. Here, we report that the zebrafish/human phosphatidylinosit...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.26362
更新日期:2017-05-02 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::The multi-domain splicing factor RBM5 regulates the balance between antagonistic isoforms of the apoptosis-control genes FAS/CD95, Caspase-2 and AID. An OCRE (OCtamer REpeat of aromatic residues) domain found in RBM5 is important for alternative splicing regulation and mediates interactions with components of the U4/U...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.14707
更新日期:2016-11-29 00:00:00
abstract::While specific mutations allow organisms to adapt to stressful environments, most changes in an organism's DNA negatively impact fitness. The mutation rate is therefore strictly regulated and often considered a slowly-evolving parameter. In contrast, we demonstrate an unexpected flexibility in cellular mutation rates ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.22939
更新日期:2017-05-02 00:00:00
abstract::Unfavorable redox conditions in the endoplasmic reticulum (ER) can decrease the capacity for protein secretion, altering vital cell functions. While systems to manage reductive stress are well-established, how cells cope with an overly oxidizing ER remains largely undefined. In previous work (Wang et al., 2014), we de...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.24141
更新日期:2017-03-03 00:00:00
abstract::Repression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 inhibit PRC2. Here, the cryo-EM structure of PRC2 on dinucleosomes reveals how binding of its catalytic subunit EZH2 to nucle...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.61964
更新日期:2020-11-19 00:00:00
abstract::Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive contro...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.12352
更新日期:2016-02-18 00:00:00
abstract::Certain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing 'leak...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.15271
更新日期:2016-05-13 00:00:00
abstract::The mechanisms generating epileptic neuronal networks following insults such as severe seizures are unknown. We have previously shown that interfering with the function of the neuron-restrictive silencer factor (NRSF/REST), an important transcription factor that influences neuronal phenotype, attenuated development of...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01267
更新日期:2014-08-12 00:00:00
abstract::Many primary sensory cilia exhibit unique architectures that are critical for transduction of specific sensory stimuli. Although basic ciliogenic mechanisms are well described, how complex ciliary structures are generated remains unclear. Seminal work performed several decades ago provided an initial but incomplete de...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01948
更新日期:2014-03-25 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::Aedes aegypti transmit pathogenic arboviruses while the mosquito itself tolerates the infection. We examine a piRNA-based immunity that relies on the acquisition of viral derived cDNA (vDNA) and how this pathway discriminates between self and non-self. The piRNAs derived from these vDNAs are essential for virus contro...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.41244
更新日期:2019-10-17 00:00:00
abstract::Recurrent somatic mutations of H3F3A in aggressive pediatric high-grade gliomas generate K27M or G34R/V mutant histone H3.3. H3.3-G34R/V mutants are common in tumors with mutations in p53 and ATRX, an H3.3-specific chromatin remodeler. To gain insight into the role of H3-G34R, we generated fission yeast that express o...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.27406
更新日期:2017-07-18 00:00:00
abstract::WW domain tandem-containing proteins such as KIBRA, YAP, and MAGI play critical roles in cell growth and polarity via binding to and positioning target proteins in specific subcellular regions. An immense disparity exists between promiscuity of WW domain-mediated target bindings and specific roles of WW domain protein...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.49439
更新日期:2019-09-05 00:00:00
abstract::How Mycobacterium tuberculosis (Mtb) rewires macrophage energy metabolism to facilitate survival is poorly characterized. Here, we used extracellular flux analysis to simultaneously measure the rates of glycolysis and respiration in real time. Mtb infection induced a quiescent energy phenotype in human monocyte-derive...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.39169
更新日期:2018-11-16 00:00:00
abstract::Unrepaired DNA damage during embryonic development can be potentially inherited by a large population of cells. However, the quality control mechanisms that minimize the contribution of damaged cells to developing embryos remain poorly understood. Here, we uncovered an ATR- and CHK1-mediated transcriptional response t...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.54756
更新日期:2020-03-12 00:00:00
abstract::The anterior cingulate cortex (ACC) encodes information supporting mnemonic and cognitive processes. We show here that a rat's position can be decoded with high spatiotemporal resolution from ACC activity. ACC neurons encoded the current state of the animal and task, except for brief excursions that sometimes occurred...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.29793
更新日期:2018-04-17 00:00:00
abstract::Numerous links exist between co-transcriptional RNA processing and the transcribing RNAPII. In particular, pre-mRNA splicing was reported to be associated with slowed RNAPII elongation. Here, we identify a site of ubiquitination (K1246) in the catalytic subunit of RNAPII close to the DNA entry path. Ubiquitination was...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.27082
更新日期:2017-10-13 00:00:00
abstract::We studied the role of the synaptic ribbon for sound encoding at the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a lack of synaptic ribbons and an assembly of several small active zones (AZs) at each ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.29275
更新日期:2018-01-12 00:00:00
abstract::Although the wiring of the cerebellar cortex appears to be uniform, the neurons in this region of the brain behave more differently from each other than previously thought. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.03285
更新日期:2014-06-10 00:00:00
abstract::Animals host multi-species microbial communities (microbiomes) whose properties may result from inter-species interactions; however, current understanding of host-microbiome interactions derives mostly from studies in which elucidation of microbe-microbe interactions is difficult. In exploring how Drosophila melanogas...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.18855
更新日期:2017-01-09 00:00:00
abstract::The time it takes a sound to travel from source to ear differs between the ears and creates an interaural delay. It varies systematically with spatial direction and is generally modeled as a pure time delay, independent of frequency. In acoustical recordings, we found that interaural delay varies with frequency at a f...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.06072
更新日期:2015-04-27 00:00:00
abstract::The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.14620
更新日期:2016-04-14 00:00:00
abstract::TMEM16F is activated by elevated intracellular Ca2+, and functions as a small-conductance ion channel and as a phospholipid scramblase. In contrast to its paralogs, the TMEM16A/B calcium-activated chloride channels, mouse TMEM16F has been reported as a cation-, anion-, or non-selective ion channel, without a definite ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45187
更新日期:2019-07-18 00:00:00
abstract::A pair of neurons is required for nematodes to be able to navigate using the Earth's magnetic field. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.09666
更新日期:2015-08-05 00:00:00
abstract::Pervasive expression of circular RNA is a recently discovered feature of eukaryotic gene expression programs, yet its function remains largely unknown. The presumed biogenesis of these RNAs involves a non-canonical 'backsplicing' event. Recent studies in mammalian cell culture posit that backsplicing is facilitated by...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.07540
更新日期:2015-06-09 00:00:00
abstract::Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infecti...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.00481
更新日期:2013-04-30 00:00:00
abstract::More than 1500 fossils from the Rising Star cave system in South Africa have been assigned to a new human species, Homo naledi, which displays a unique combination of primitive and derived traits throughout the skeleton. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.10627
更新日期:2015-09-10 00:00:00
abstract::Previous studies had shown that the integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mou...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.15614
更新日期:2016-09-13 00:00:00