Abstract：
:The auditory inner hair cell (IHC) ribbon synapse operates with an exceptional temporal precision and maintains a high level of neurotransmitter release. However, the molecular mechanisms underlying IHC synaptic exocytosis are largely unknown. We studied otoferlin, a predicted C2-domain transmembrane protein, which is defective in a recessive form of human deafness. We show that otoferlin expression in the hair cells correlates with afferent synaptogenesis and find that otoferlin localizes to ribbon-associated synaptic vesicles. Otoferlin binds Ca(2+) and displays Ca(2+)-dependent interactions with the SNARE proteins syntaxin1 and SNAP25. Otoferlin deficient mice (Otof(-/-)) are profoundly deaf. Exocytosis in Otof(-/-) IHCs is almost completely abolished, despite normal ribbon synapse morphogenesis and Ca(2+) current. Thus, otoferlin is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the IHC ribbon synapse.
journal_name
Celljournal_title
Cellauthors
Roux I,Safieddine S,Nouvian R,Grati M,Simmler MC,Bahloul A,Perfettini I,Le Gall M,Rostaing P,Hamard G,Triller A,Avan P,Moser T,Petit Cdoi
10.1016/j.cell.2006.08.040subject
Has Abstractpub_date
2006-10-20 00:00:00pages
277-89issue
2eissn
0092-8674issn
1097-4172pii
S0092-8674(06)01218-9journal_volume
127pub_type
杂志文章相关文献
CELL文献大全abstract：:We have reproduced the posttranslational mode of protein translocation across the endoplasmic reticulum membrane with reconstituted proteoliposomes containing a purified complex of seven yeast proteins. This Sec complex includes a heterotrimeric Sec61p complex, homologous to that in mammals, as well as all other membr...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(95)90077-2
更新日期：1995-05-19 00:00:00
abstract：:Microbial populations can maximize fitness in dynamic environments through bet hedging, a process wherein a subpopulation assumes a phenotype not optimally adapted to the present environment but well adapted to an environment likely to be encountered. Here, we show that oxygen induces fluctuating expression of the tri...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2018.02.005
更新日期：2018-03-22 00:00:00
abstract：:Angiogenesis is an important event for embryonic organogenesis as well as for tissue repair in the adult. Here, we show that hematopoietic stem cells (HSCs) play important roles for angiogenesis during embryogenesis. To investigate the role of HSCs in endothelial cell (EC) development, we analyzed AML1-deficient embry...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)00025-8
更新日期：2000-07-21 00:00:00
abstract：:Treatment of guinea pig neutrophils with pertussis toxin (islet-activating protein; IAP) results in inhibition of N-formyl peptide receptor-mediated release of arachidonic acid and granular enzymes. Inhibition by the toxin is specific, in that responses to the calcium ionophore A23187 are not affected. The action of t...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(84)90008-4
更新日期：1984-12-01 00:00:00
abstract：:A family of novel substrates was designed to enable the efficient accumulation of intermediates in site-specific recombination. Strategically placed nicks allow these "suicide substrates" to initiate the reaction but prevent its completion or reversal. Consequently, it has been possible to determine that lambda site-s...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(87)90336-9
更新日期：1987-08-28 00:00:00
abstract：:Cellular ras activity has been neutralized in 3T3 cells by microinjection of a specific anti-ras monoclonal antibody. The injected antibody efficiently inhibited proliferation in cells treated with a phorbol ester and a calcium ionophore, or with prostaglandin F2 alpha. These treatments were designed to imitate the ac...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(88)90531-4
更新日期：1988-01-15 00:00:00
abstract：:Increased protein synthesis plays an etiologic role in diverse cancers. Here, we demonstrate that METTL13 (methyltransferase-like 13) dimethylation of eEF1A (eukaryotic elongation factor 1A) lysine 55 (eEF1AK55me2) is utilized by Ras-driven cancers to increase translational output and promote tumorigenesis in vivo. ME...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2018.11.038
更新日期：2019-01-24 00:00:00
abstract：:We have characterized a nondifferentiating mouse muscle cell line, NFB, that represses the activity of the helix-loop-helix (HLH) family of myogenic regulators, yet expresses sarcomeric actins. The NFB MyoD gene is silent, but can be activated upon transfection of a long terminal region-controlled chicken MyoD cDNA, r...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(90)90014-6
更新日期：1990-08-10 00:00:00
abstract：:We have investigated RNA recombination among poliovirus genomes by analyzing both intratypic and intertypic recombinant crosses involving the same defined genetic markers. Sequence analysis of the recombinant junctions of 13 nonsibling intertypic recombinants showed that intertypic RNA recombination is not site-specif...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(86)90600-8
更新日期：1986-11-07 00:00:00
abstract：:NRK fibroblasts exposed to transforming growth factor-beta (TGF-beta) show increased binding of radiolabeled epidermal growth factor (EGF) relative to untreated cells. The binding of another growth factor, rat insulin-like growth factor-II, is unaffected. The increase in EGF binding induced by TGF-beta is not due to i...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(84)90071-0
更新日期：1984-01-01 00:00:00
abstract：:Circadian rhythms control organismal physiology throughout the day. At the cellular level, clock regulation is established by a self-sustained Bmal1-dependent transcriptional oscillator network. However, it is still unclear how different tissues achieve a synchronized rhythmic physiology. That is, do they respond inde...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2019.05.009
更新日期：2019-05-30 00:00:00
abstract：:The Drosha-DGCR8 complex, also known as Microprocessor, is essential for microRNA (miRNA) maturation. Drosha functions as the catalytic subunit, while DGCR8 (also known as Pasha) recognizes the RNA substrate. Although the action mechanism of this complex has been intensively studied, it remains unclear how Drosha and ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2008.10.053
更新日期：2009-01-09 00:00:00
abstract：:Excessive sun tanning can result in addictive behavior. In this issue of Cell, Fell et al. utilize a combination of behavioral pharmacology and transgenic mice to demonstrate that chronic UV light exposure recruits p53 signaling in keratinocytes, subsequently increasing β-endorphin signaling at opioid receptors, and p...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2014.06.009
更新日期：2014-06-19 00:00:00
abstract：:The mechanisms of transcriptional activation in heterochromatin were investigated by using FISH to directly visualize changes in chromatin organization during activation of a heterochromatic lambda5 transgene. A DNase I hypersensitive site was shown to relocate the transgene to the outside of the pericentromeric heter...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)00177-x
更新日期：2000-11-22 00:00:00
abstract：:STAT6 plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines. We now show that STAT6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger STING (also named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2011.09.022
更新日期：2011-10-14 00:00:00
abstract：:Release of CHO-K1 cells from plateau or stationary phase and reentry into the cell cycle is specifically and reversibly blocked at two distinct sites by the anticalmodulin drug W13. The first block occurs early during release while the cells are still at G0/G1, whereas the second occurs later in reentry during early S...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(84)90075-8
更新日期：1984-01-01 00:00:00
abstract：:Glucose homeostasis is strictly controlled in all domains of life. Bacteria that are unable to balance intracellular sugar levels and deal with potentially toxic phosphosugars cease growth and risk being outcompeted. Here, we identify the conserved haloacid dehalogenase (HAD)-like enzyme YigL as the previously hypothe...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2013.03.003
更新日期：2013-04-11 00:00:00
abstract：:Transposons evolve rapidly and can mobilize and trigger genetic instability. Piwi-interacting RNAs (piRNAs) silence these genome pathogens, but it is unclear how the piRNA pathway adapts to invasion of new transposons. In Drosophila, piRNAs are encoded by heterochromatic clusters and maternally deposited in the embryo...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2011.11.042
更新日期：2011-12-23 00:00:00
abstract：:In this issue of Cell, Shin et al. report the first live-cell imaging of a fusion pore. Directly visualized pores in neuroendocrine cells can be much larger than expected yet not require vesicular full-collapse. These fusion-fission pores have diverse fates arising from opposing dynamin-driven pore constriction and F-...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2018.04.016
更新日期：2018-05-03 00:00:00
abstract：:Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target sites and function together to form repressive chromatin domains remain po...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2014.05.004
更新日期：2014-06-05 00:00:00
abstract：:The state and organization of viral DNA sequences present in independently isolated rat cell lines transformed with SV40 were investigated using restriction-enzyme cleavage of the cellular DNA and blot hybridization with a viral probe. The transformed lines were established under conditions as identical as possible, e...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(80)90569-3
更新日期：1980-12-01 00:00:00
abstract：:In two companion reports, the TRACERx consortium investigates tumor heterogeneity and evolution in early-stage non-small cell lung cancer. The studies highlight the prognostic value of copy-number heterogeneity assessment in tumor biopsies and circulating tumor DNA detection in plasma and suggest that tracking the evo...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2017.05.001
更新日期：2017-05-18 00:00:00
abstract：:A nutritious diet low in calories improves the health and extends the life span of rodents. Recent studies identified a gene, SIR2, which encodes an NAD-dependent deacetylase and may mediate the effects of calorie restriction. In this review, we discuss SIR2 genes and calorie restriction in the lower organisms yeast a...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2005.01.029
更新日期：2005-02-25 00:00:00
abstract：:Drosophila chorion genes are located in two clusters, one on the X chromosome at 7F1-2 of the polytene chromosome map and a second on the third chromosome at 66D11-15. Genes in both regions undergo amplification in ovarian follicle cells prior to their expression late in oogenesis. Analysis of cloned genomic segments ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(81)90373-1
更新日期：1981-11-01 00:00:00
abstract：:Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating t...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2017.11.010
更新日期：2018-01-11 00:00:00
abstract：:During Tetrahymena conjugation, programmed DNA degradation occurs in two separate nuclei. Thousands of germline-specific deletion elements are removed from the genome of the developing somatic macronucleus, and the old parental macronucleus is degraded by an apoptotic mechanism. An abundant polypeptide, Pdd1p (formerl...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81324-0
更新日期：1996-10-04 00:00:00
abstract：:We have isolated five clones containing human histone genes from a human genomic DNA library, using a cloned X. laevis histone H4 cDNA probe (pX1ch4). Each genomic clone has been mapped and the locations of the histone genes have been determined by blot hybridization and hybridization-selection of human histone mRNA. ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(81)90092-1
更新日期：1981-06-01 00:00:00
abstract：:Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan re...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2014.03.012
更新日期：2014-03-27 00:00:00
abstract：:Forms of RNA polymerase I prepared from growing or encysted Acanthamoeba are equal in the ability to transcribe poly(dl:dC). Polymerase from cysts, whose rRNA genes are transcriptionally inactive, is unable to utilize the rDNA promoter in vitro, whereas the transcription initiation factor from cysts is fully able to b...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(86)90601-x
更新日期：1986-11-07 00:00:00
abstract：:The mitochondrial RNA binding proteins MRP1 and MRP2 form a heteromeric complex that functions in kinetoplastid RNA editing. In this process, MRP1/MRP2 serves as a matchmaker by binding to guide RNAs and facilitating their hybridization with cognate preedited mRNAs. To understand the mechanism by which this complex pe...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2006.06.047
更新日期：2006-08-25 00:00:00
