Abstract:
:To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.
journal_name
Elifejournal_title
eLifeauthors
Höglinger D,Haberkant P,Aguilera-Romero A,Riezman H,Porter FD,Platt FM,Galione A,Schultz Cdoi
10.7554/eLife.10616subject
Has Abstractpub_date
2015-11-27 00:00:00issn
2050-084Xjournal_volume
4pub_type
杂志文章相关文献
eLife文献大全abstract::Long noncoding RNAs (lncRNAs) have been shown to act as important cell biological regulators including cell fate decisions but are often ignored in human genetics. Combining differential lncRNA expression during neuronal lineage induction with copy number variation morbidity maps of a cohort of children with autism sp...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.41770
更新日期:2019-01-10 00:00:00
abstract::Organisms possessing genetic codes with unassigned codons raise the question of how cellular machinery resolves such codons and how this could impact horizontal gene transfer. Here, we use a genomically recoded Escherichia coli to examine how organisms address translation at unassigned UAG codons, which obstruct propa...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34878
更新日期:2018-10-30 00:00:00
abstract::In plants the dorsoventral boundary of leaves defines an axis of symmetry through the centre of the organ separating the top (dorsal) and bottom (ventral) tissues. Although the positioning of this boundary is critical for leaf morphogenesis, how the boundary is established and how it influences development remains unc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.27421
更新日期:2017-09-12 00:00:00
abstract::Peptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that se...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56048
更新日期:2020-05-29 00:00:00
abstract::Researchers have identified two genes-follistatin and activin-as having an important role in the ability of certain flatworms to identify wounds that require the production of new tissue. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.00533
更新日期:2013-09-10 00:00:00
abstract::The expansion of bacterial swarms and the spreading of biofilms can be described by a unified biophysical theory that involves both active and passive processes. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47019
更新日期:2019-04-30 00:00:00
abstract::R-loops are features of chromatin consisting of a strand of DNA hybridized to RNA, as well as the expelled complementary DNA strand. R-loops are enriched at promoters where they have recently been shown to have important roles in modifying gene expression. However, the location of promoter-associated R-loops and the g...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.28306
更新日期:2017-10-26 00:00:00
abstract::During early embryogenesis, cells must exit pluripotency and commit to multiple lineages in all germ-layers. How this transition is operated in vivo is poorly understood. Here, we report that MEK1 and the Nanog-related transcription factor Ventx2 coordinate this transition. MEK1 was required to make Xenopus pluripoten...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.21526
更新日期:2017-06-27 00:00:00
abstract::Bacterial flagella mediate host-microbe interactions through tissue tropism during colonization, as well as by activating immune responses. The flagellar shaft of some bacteria, including several human pathogens, is encased in a membranous sheath of unknown function. While it has been hypothesized that the sheath may ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01579
更新日期:2014-03-04 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::Being exposed to cannabinoids in the womb has different consequences for male and female rats. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.41229
更新日期:2018-09-28 00:00:00
abstract::Temporal patterning of neural progenitors leads to the sequential production of diverse neurons. To understand how extrinsic cues influence intrinsic temporal programs, we studied Drosophila mushroom body progenitors (neuroblasts) that sequentially produce only three neuronal types: γ, then α'β', followed by αβ. Oppos...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.58880
更新日期:2020-07-06 00:00:00
abstract::Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest know...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03743
更新日期:2014-12-11 00:00:00
abstract::Some cortical neurons receive highly selective thalamocortical (TC) input, but others do not. Here, we examine connectivity of single thalamic neurons (lateral geniculate nucleus, LGN) onto putative fast-spike inhibitory interneurons in layer 4 of rabbit visual cortex. We show that three 'rules' regulate this connecti...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.60102
更新日期:2020-12-08 00:00:00
abstract::Probabilistic models of adaptive immune repertoire sequence distributions can be used to infer the expansion of immune cells in response to stimulus, differentiate genetic from environmental factors that determine repertoire sharing, and evaluate the suitability of various target immune sequences for stimulation via v...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46935
更新日期:2019-09-05 00:00:00
abstract::The germ line provides the cellular link between generations of multicellular organisms, its cells entering the meiotic cell cycle only once each generation. However, the mechanisms governing this initiation of meiosis remain poorly understood. Here, we examined cells undergoing meiotic initiation in mice, and we foun...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.43738
更新日期:2019-02-27 00:00:00
abstract::Experience-dependent reorganisation of functional maps in the cerebral cortex is well described in the primary sensory cortices. However, there is relatively little evidence for such cortical reorganisation over the short-term. Using human somatosensory cortex as a model, we investigated the effects of a 24 hr gluing ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.17280
更新日期:2016-12-30 00:00:00
abstract::Genome-wide association analyses have uncovered multiple genomic regions associated with T2D, but identification of the causal variants at these remains a challenge. There is growing interest in the potential of deep learning models - which predict epigenome features from DNA sequence - to support inference concerning...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.51503
更新日期:2020-01-27 00:00:00
abstract::Two different cell signals often affect transcription of the same gene. In such cases, it is natural to ask how the combined transcriptional response compares to the individual responses. The most commonly used mechanistic models predict additive or multiplicative combined responses, but a systematic genome-wide evalu...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.59388
更新日期:2020-12-07 00:00:00
abstract::RNA molecules cause the proteins involved in the formation of germ granules to coalesce into liquid droplets. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.24106
更新日期:2017-01-24 00:00:00
abstract::Using a common analysis pipeline to compare data from three major lineages of complex eukaryotes reveals that transcription seems to evolve at a common rate. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.14150
更新日期:2016-02-11 00:00:00
abstract::Even when we are at rest, our spinal cords show spontaneous, yet well organised, fluctuations of activity that might reflect sensory and motor networks. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.03811
更新日期:2014-08-05 00:00:00
abstract::Stem cells are maintained in a specialized microenvironment called niche but the nature of stem cell niche remains poorly defined in many systems. Here we demonstrate that intestinal epithelium-derived BMP serves as a niche signal for intestinal stem cell (ISC) self-renewal in Drosophila adult midgut. We find that BMP...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01857
更新日期:2014-03-11 00:00:00
abstract::Whether neurons encode information through their spike rates, their activity times or both is an ongoing debate in systems neuroscience. Here, we tested whether humans can discriminate between a pair of temporal odor mixtures (TOMs) composed of the same two components delivered in rapid succession in either one tempor...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.49734
更新日期:2020-02-07 00:00:00
abstract::Transient receptor potential (TRP) ion channels in peripheral sensory neurons are functionally regulated by hydrolysis of the phosphoinositide PI(4,5)P2 and changes in the level of protein kinase mediated phosphorylation following activation of various G protein coupled receptors. We now show that the activity of TRPM...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.26138
更新日期:2017-08-15 00:00:00
abstract::Protein synthesis ends when a ribosome reaches an mRNA stop codon. Release factors (RFs) decode the stop codon, hydrolyze peptidyl-tRNA to release the nascent protein, and then dissociate to allow ribosome recycling. To visualize termination by RF2, we resolved a cryo-EM ensemble of E. coli 70S•RF2 structures at up to...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46850
更新日期:2019-09-12 00:00:00
abstract::Toxoplasma gondii contains a limited subset of actin binding proteins. Here we show that the putative actin regulator cyclase-associated protein (CAP) is present in two different isoforms and its deletion leads to significant defects in some but not all actin dependent processes. We observe defects in cell-cell commun...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.50598
更新日期:2019-10-02 00:00:00
abstract::Aging is an intricate phenomenon associated with the gradual loss of physiological functions, and both nutrient sensing and proteostasis control lifespan. Although multiple approaches have facilitated the identification of candidate genes that govern longevity, the molecular mechanisms that link aging pathways are sti...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.39925
更新日期:2018-12-05 00:00:00
abstract::Disturbance from whale-watching can cause significant behavioural changes with fitness consequences for targeted whale populations. However, the sensory stimuli triggering these responses are unknown, preventing effective mitigation. Here, we test the hypothesis that vessel noise level is a driver of disturbance, usin...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56760
更新日期:2020-06-16 00:00:00
abstract::In eukaryotes, intra-chromosomal recombination generates DNA circles, but little is known about how cells react to them. In yeast, partitioning of such circles to the mother cell at mitosis ensures their loss from the population but promotes replicative ageing. Nevertheless, the mechanisms of partitioning are debated....
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03790
更新日期:2014-11-17 00:00:00