Abstract:
:Intracellular Ca(2+) release in many types of cells is mediated by ryanodine receptor Ca(2+) release channels (RyRCs) that are assembled into two-dimensional paracrystalline arrays in the endoplasmic/sarcoplasmic reticulum. However, the in situ operating mechanism of the RyRC array is unknown. Here, we found that the elementary Ca(2+) release events, Ca(2+) sparks from individual RyRC arrays in rat ventricular myocytes, exhibit quantized Ca(2+) release flux. Analysis of the quantal property of Ca(2+) sparks provided a view of unitary Ca(2+) current and gating kinetics of the RyRC in intact cells and revealed that spark activation involves dynamic recruitment of small, variable cohorts of RyRCs. Intriguingly, interplay of RyRCs in multichannel sparks renders an unusual, thermodynamically irreversible mode of channel gating that is unshared by an RyRC acting solo, nor by RyRCs in vitro. Furthermore, an array-based inhibitory feedback, overriding the regenerative Ca(2+)-induced Ca(2+) release of RyRCs, provides a supramolecular mechanism for the microscopic stability of intracellular Ca(2+) signaling.
journal_name
Proc Natl Acad Sci U S Aauthors
Wang SQ,Stern MD,Ríos E,Cheng Hdoi
10.1073/pnas.0306157101keywords:
subject
Has Abstractpub_date
2004-03-16 00:00:00pages
3979-84issue
11eissn
0027-8424issn
1091-6490pii
0306157101journal_volume
101pub_type
杂志文章abstract::The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. The coronavirus spike (S) glycoprotein initiates infection by promoting fusion of the viral and cellular membranes through conformational changes that remain largely uncharacte...
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.1708727114
更新日期:2017-10-17 00:00:00
abstract::Flow separation and vortex shedding are some of the most common phenomena experienced by bluff bodies under relative motion with the surrounding medium. They often result in a recirculation bubble in regions with adverse pressure gradient, which typically reduces efficiency in vehicles and increases loading on structu...
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.1715567115
更新日期:2018-02-06 00:00:00
abstract::Bloom syndrome (BS) is a rare cancer-predisposing disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. BLM, the protein altered in BS, is a RecQ DNA helicase. This report shows that BLM is found in the nucleus of normal human cells in the nuclear domain 10 ...
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.090525897
更新日期:2000-05-09 00:00:00
abstract::A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < ...
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.0605832103
更新日期:2006-09-19 00:00:00
abstract::It has been found that the mutator phenotype of the recA441 and recA730 strains that express the SOS response constitutively is suppressed by pIP1, a high-copy plasmid carrying the dnaQ gene encoding the 3'----5' exonuclease subunit (epsilon) of DNA polymerase III. We have constructed plasmid pIP11, in which the dnaQ ...
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.85.23.9124
更新日期:1988-12-01 00:00:00
abstract::A single-chain Fv (scFv) fusion phage library derived from random combinations of VH and VL (variable heavy and light chains) domains in the antibody repertoire of a vaccinated melanoma patient was previously used to isolate clones that bind specifically to melanoma cells. An unexpected finding was that one of the clo...
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.94.17.9261
更新日期:1997-08-19 00:00:00
abstract::Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the CNS that causes disability in young adults as a result of the irreversible accumulation of neurological deficits. Although there are potent disease-modifying agents for its initial relapsing-remitting phase, these therapies show limited...
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.1615413114
更新日期:2017-02-21 00:00:00
abstract::The study of photoinitiated electron transfer in donor-bridge-acceptor molecules has helped elucidate the distance dependence of electron transfer rates and behavior of various electron transfer mechanisms. In all reported cases, the energies of the bridge electronic states involved in the electron transfer change dra...
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.0408940102
更新日期:2005-03-08 00:00:00
abstract::Growth of 3T3-L2 fibroblasts in medium containing 5-bromo-2'-deoxyuridine prevents the spontaneous cytodifferentiation of these cells into adipose cells. Treatment of bromodeoxyuridine-suppressed cultures at confluence with 1-methyl-3-isobutylxanthine, a promoter of the adipose conversion, results in differentiation o...
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.76.9.4451
更新日期:1979-09-01 00:00:00
abstract::The cell surface of embryonic peripheral neurons provides a mitogenic stimulus for Schwann cells. We report (i) the solubilization of this mitogenic activity from rat dorsal root ganglion neurons grown in tissue culture and (ii) the solubilization and partial purification of mitogenic activity from neonatal rat brains...
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.85.18.6992
更新日期:1988-09-01 00:00:00
abstract::Prions are composed solely of an alternatively folded isoform of the prion protein (PrP), designated PrP(Sc). N-terminally truncated PrP(Sc), denoted PrP 27-30, retains infectivity and polymerizes into rods with the ultrastructural and tinctorial properties of amyloid. We report here that some polyoxometalates (POMs) ...
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.0812770106
更新日期:2009-03-10 00:00:00
abstract::Imaging membranes in live cells with nanometer-scale resolution promises to reveal ultrastructural dynamics of organelles that are essential for cellular functions. In this work, we identified photoswitchable membrane probes and obtained super-resolution fluorescence images of cellular membranes. We demonstrated the p...
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.1201882109
更新日期:2012-08-28 00:00:00
abstract::The chemosmotic model provides a framework for visualizing energy-coupled reactions (vectorial reaction sequences, membrane-dependent gradient formation, and charge separation of reacting species) and a mechanism for energy coupling (indirect coupling between the driving and driven reaction sequences mediated by a mem...
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.78.4.2240
更新日期:1981-04-01 00:00:00
abstract::Quantitative immunohistochemical analysis of the sphenopalatine ganglion in normal cats revealed that virtually all ganglion cells (98.5%) were immunoreactive to vasoactive intestinal polypeptide (VIP). After surgical removal of this ganglion, the content of both VIP and choline acetyltransferase (acetyl-CoA:choline O...
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.78.8.5255
更新日期:1981-08-01 00:00:00
abstract::We evaluated the formation and removal of (+-)-3 alpha,4 beta-dihydroxy-1 alpha,2 alpha-epoxy-1,2,3,4- tetrahydrobenzo[c]phenanthrene (BcPHDE)-DNA adducts in two Chinese hamster ovary (CHO) cell lines. One line of repair-proficient cells (MK42) carries a stable 150-fold amplification of the dihydrofolate reductase (DH...
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.89.24.11925
更新日期:1992-12-15 00:00:00
abstract::A typical homing endonuclease initiates mobility of its group I intron by recognizing DNA both upstream and downstream of the intron insertion site of intronless alleles, preventing the endonuclease from binding and cleaving its own intron-containing allele. Here, we describe a GIY-YIG family homing endonuclease, I-Bm...
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.141222498
更新日期:2001-07-03 00:00:00
abstract::Heat-shock protein of 90 kDa (Hsp90) is an essential molecular chaperone that adopts different 3D structures associated with distinct nucleotide states: a wide-open, V-shaped dimer in the apo state and a twisted, N-terminally closed dimer with ATP. Although the N domain is known to mediate ATP binding, how Hsp90 sense...
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.1516167113
更新日期:2016-03-15 00:00:00
abstract::Efficient single nucleotide polymorphism (SNP) genotyping methods are necessary to accomplish many current gene discovery goals. A crucial element in large-scale SNP genotyping is the number of individual biochemical reactions that must be performed. An efficient method that can be used to simultaneously amplify a set...
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.261710699
更新日期:2002-03-05 00:00:00
abstract::Serotonin (5-hydroxytryptamine; 0.5 microM and above) stimulated the synthesis of prostacyclin (as measured by radioimmunoassay of 6-ketoprostaglandin F1 alpha) by bovine aortic smooth muscle cells in culture. This effect was structurally specific; a similar response was not elicited by the other indoles (tryptophan, ...
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.78.11.7134
更新日期:1981-11-01 00:00:00
abstract::The first step in the formation of the protease resistant form (PrPSc) of prion proteins involves a conformational transition of the monomeric cellular form of PrPC to a more stable aggregation prone state PrPC*. A search of PDBselect and Escherichia coli and yeast genomes shows that the exact pattern of charges in he...
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.0404235101
更新日期:2004-10-26 00:00:00
abstract::Echoviruses have been implicated in multiple human disease syndromes, including aseptic meningitis, paralysis, and heart disease, but no animal model is available for studying the pathogenesis of infection. Production of human integrin very late antigen 2, a receptor for echovirus type 1, in transgenic mice conferred ...
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.2535934100
更新日期:2003-12-23 00:00:00
abstract::We previously reported that long-term cyclic estrogen (E) treatment reverses age-related impairment of cognitive function mediated by the dorsolateral prefrontal cortex (dlPFC) in ovariectomized (OVX) female rhesus monkeys, and that E induces a corresponding increase in spine density in layer III dlPFC pyramidal neuro...
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.0704757104
更新日期:2007-07-03 00:00:00
abstract::An RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) has been purified from phage-SP01-infected Bacillus subtilis that copies RNA almost exclusively from the heavy strand of native SP01 DNA, the DNA strand from which "middle" and "late" classes of RNA are copied in vivo. Hybridization-com...
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.72.4.1589
更新日期:1975-04-01 00:00:00
abstract::Cytochrome c maturation in Escherichia coli requires the ccm operon, which encodes eight membrane proteins (CcmABCDEFGH). CcmE is a periplasmic heme chaperone that binds heme covalently and transfers it onto apocytochrome c in the presence of CcmF, CcmG, and CcmH. In this work we addressed the functions of the ccmABCD...
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.96.11.6462
更新日期:1999-05-25 00:00:00
abstract::Mechanisms of estrogen-induced tumorigenesis in the target organ are not well understood. It has been suggested that oxidative stress resulting from metabolic activation of carcinogenic estrogens plays a critical role in estrogen-induced carcinogenesis. We tested this hypothesis by using an estrogen-induced hamster re...
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.0437929100
更新日期:2003-04-01 00:00:00
abstract::Border cell migration is a stereotyped migration occurring during the development of the Drosophila egg chamber. During this process, a cluster composed of six to eight follicle cells migrates between nurse cells toward the oocyte. Receptor tyrosine kinases (RTKs) are enriched at the leading edge of the follicle 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.1010795108
更新日期:2010-12-28 00:00:00
abstract::In the presence of the S polypeptide, maize chloroplast DNA-dependent RNA polymerase preferentially transcribes sequences within the 2200-nucleotide-pair-long maize chloroplast chromosome fragment Eco [unk] from a supercoiled chimeric plasmid cloned in Escherichia coli [Jolly, S. O. & Bogorad, L. (1980) Proc. Natl. Ac...
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.78.6.3423
更新日期:1981-06-01 00:00:00
abstract::Genotype-phenotype relationships are notoriously complicated. Idiosyncratic interactions between specific combinations of mutations occur and are difficult to predict. Yet it is increasingly clear that many interactions can be understood in terms of global epistasis. That is, mutations may act additively on some under...
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.1804015115
更新日期:2018-08-07 00:00:00
abstract::The transcription of genes encoding gluconeogenic enzymes is tightly regulated during the perinatal period. These genes are induced by glucagon (cAMP) and glucocorticoids and repressed by insulin. To address the role of cAMP and glucocorticoids in the physiological activation of genes encoding gluconeogenic enzymes in...
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.92.10.4244
更新日期:1995-05-09 00:00:00
abstract::RNA-binding motif protein 4 (RBM4) plays a regulatory role in alternative splicing of precursor mRNA. We show here that cell stress such as arsenite exposure induces phosphorylation of RBM4 at serine 309 and also drives its cytoplasmic accumulation and targeting to stress granule via the MKK(3/6)-p38 signaling pathway...
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.0611015104
更新日期:2007-02-13 00:00:00