Abstract：
:Missense mutations in Valosin-Containing Protein (VCP) are linked to diverse degenerative diseases including IBMPFD, amyotrophic lateral sclerosis (ALS), muscular dystrophy and Parkinson's disease. Here, we characterize a VCP-binding co-factor (SVIP) that specifically recruits VCP to lysosomes. SVIP is essential for lysosomal dynamic stability and autophagosomal-lysosomal fusion. SVIP mutations cause muscle wasting and neuromuscular degeneration while muscle-specific SVIP over-expression increases lysosomal abundance and is sufficient to extend lifespan in a context, stress-dependent manner. We also establish multiple links between SVIP and VCP-dependent disease in our Drosophila model system. A biochemical screen identifies a disease-causing VCP mutation that prevents SVIP binding. Conversely, over-expression of an SVIP mutation that prevents VCP binding is deleterious. Finally, we identify a human SVIP mutation and confirm the pathogenicity of this mutation in our Drosophila model. We propose a model for VCP disease based on the differential, co-factor-dependent recruitment of VCP to intracellular organelles.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Johnson AE,Orr BO,Fetter RD,Moughamian AJ,Primeaux LA,Geier EG,Yokoyama JS,Miller BL,Davis GWdoi
10.1038/s41467-020-20796-8subject
Has Abstractpub_date
2021-01-21 00:00:00pages
513issue
1issn
2041-1723pii
10.1038/s41467-020-20796-8journal_volume
12pub_type
杂志文章abstract：:Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatm...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms14152
更新日期：2017-01-20 00:00:00
abstract：:Topological insulators interacting with magnetic impurities have been reported to host several unconventional effects. These phenomena are described within the framework of gapping Dirac quasiparticles due to broken time-reversal symmetry. However, the overwhelming majority of studies demonstrate the presence of a fin...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms12027
更新日期：2016-06-27 00:00:00
abstract：:Aqueous nanofibres constructed by the self-assembly of small amphiphilic molecules can become entangled to form hydrogels that have a variety of applications including tissue engineering, and controlled drug delivery. The hydrogels are formed through the random physical cross-linkings of flexible nanofibres. Here we r...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms1465
更新日期：2011-09-06 00:00:00
abstract：:The electron deficiency and strong bonding capacity of boron have led to a vast variety of molecular structures in chemistry and materials science. Here we report the observation of highly symmetric cobalt-centered boron drum-like structures of CoB16(-), characterized by photoelectron spectroscopy and ab initio calcul...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms9654
更新日期：2015-10-12 00:00:00
abstract：:Jasmonic acid (JA) is well known to promote lateral root formation but the mechanisms by which JA signalling is integrated into the pathways responsible for lateral root formation, and how it interacts with auxin in this process remains poorly understood. Here, we report that the highly JA-responsive ethylene response...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms6833
更新日期：2014-12-19 00:00:00
abstract：:Discharge from sliding outlet glaciers controls uncertainty in projections for future sea level. Remarkably, over 90% of glacial area is subject to gravitational driving stresses below 150 kPa (median ∼70 kPa). Longstanding explanations that appeal to the shear-thinning rheology of ice tend to overpredict driving stre...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-05716-1
更新日期：2018-08-13 00:00:00
abstract：:The Mycobacterium tuberculosis (Mtb) electron transport chain (ETC) has received significant attention as a drug target, however its vulnerability may be affected by its flexibility in response to disruption. Here we determine the effect of the ETC inhibitors bedaquiline, Q203 and clofazimine on the Mtb ETC, and the v...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms12393
更新日期：2016-08-10 00:00:00
abstract：:The global urbanization rate is accelerating; however, data limitations have far prevented robust estimations of either global urban expansion or its effects on terrestrial net primary productivity (NPP). Here, using a high resolution dataset of global land use/cover (GlobeLand30), we show that global urban areas expa...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-13462-1
更新日期：2019-12-05 00:00:00
abstract：:Self-induced electricity, including lightning, is often observed in dusty atmospheres. However, the physical mechanisms leading to this phenomenon remain elusive as they are remarkably challenging to determine due to the high complexity of the multi-phase turbulent flows involved. Using a fast multi-pole method in dir...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-03958-7
更新日期：2018-04-26 00:00:00
abstract：:Microbial fatty acid-derived fuels have emerged as promising alternatives to petroleum-based transportation fuels. Here we report a modular engineering approach that systematically removed metabolic pathway bottlenecks and led to significant titre improvements in a multi-gene fatty acid metabolic pathway. On the basis...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms2425
更新日期：2013-01-01 00:00:00
abstract：:Calcareous microplankton shells form the dominant components of ancient and modern pelagic sea-floor carbonates and are widely used in palaeoenvironmental reconstructions. The efficacy of these applications, however, is dependent upon minimal geochemical alteration during diagenesis, but these modifying processes are ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms3052
更新日期：2013-01-01 00:00:00
abstract：:In adult skin epidermis and the epithelium lining the esophagus cells are constantly shed from the tissue surface and replaced by cell division. Tracking genetically labelled cells in transgenic mice has given insight into cell behavior, but conflicting models appear consistent with the results. Here, we use an additi...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-15258-0
更新日期：2020-03-18 00:00:00
abstract：:Materials with switchable absorption properties have been widely used for smart window applications to reduce energy consumption and enhance occupant comfort in buildings. In this work, we combine the benefits of smart windows with energy conversion by producing a photovoltaic device with a switchable absorber layer t...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-017-01842-4
更新日期：2017-11-23 00:00:00
abstract：:The rice blast fungus Magnaporthe oryzae is a model for studying fungal-plant interactions. Although it produces two types of spores (microconidia and macroconidia), previous infection studies have exclusively dealt with macroconidia. Germination of microconidia has not been reported, and their role in plant infection...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms5518
更新日期：2014-08-01 00:00:00
abstract：:Despite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungar...
journal_title：Nature communications
pub_type： 历史文章,杂志文章
doi：10.1038/s41467-018-06024-4
更新日期：2018-09-11 00:00:00
abstract：:Molecules can efficiently and selectively convert light energy into other degrees of freedom. Disentangling the underlying ultrafast motion of electrons and nuclei of the photoexcited molecule presents a challenge to current spectroscopic approaches. Here we explore the photoexcited dynamics of molecules by an interac...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms5235
更新日期：2014-06-23 00:00:00
abstract：:Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chiT-bet+ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients,...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-03750-7
更新日期：2018-05-01 00:00:00
abstract：:It has been suggested that deficient protein trafficking to the cell membrane is the dominant mechanism associated with type 2 Long QT syndrome (LQT2) caused by Kv11.1 potassium channel missense mutations, and that for many mutations the trafficking defect can be corrected pharmacologically. However, this inference wa...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms6535
更新日期：2014-11-24 00:00:00
abstract：:The social intelligence hypothesis (SIH) posits that within-group interactions drive cognitive evolution, but it has received equivocal support. We argue the SIH overlooks a major component of social life: interactions with conspecific outsiders. Competition for vital resources means conspecific outsiders present myri...
journal_title：Nature communications
pub_type： 杂志文章,评审
doi：10.1038/s41467-020-18780-3
更新日期：2020-10-06 00:00:00
abstract：:Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-08844-4
更新日期：2019-03-04 00:00:00
abstract：:Breaking time-reversal symmetry enables the realization of non-reciprocal devices, such as isolators and circulators, of fundamental importance in microwave and photonic communication systems. This effect is almost exclusively achieved today through magneto-optical phenomena, which are incompatible with integrated tec...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms3407
更新日期：2013-01-01 00:00:00
abstract：:A superconducting state is characterized by the gap in the electronic density of states, which vanishes at the superconducting transition temperature T(c). It was discovered that in high-temperature superconductors, a noticeable depression in the density of states, the pseudogap, still remains even at temperatures abo...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms1140
更新日期：2010-01-01 00:00:00
abstract：:To expand the toolbox of imaging in living cells, we have engineered a single-chain variable fragment binding the linear HA epitope with high affinity and specificity in vivo. The resulting probe, called the HA frankenbody, can light up in multiple colors HA-tagged nuclear, cytoplasmic, membrane, and mitochondrial pro...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-10846-1
更新日期：2019-07-03 00:00:00
abstract：:Developmental plasticity describes the influence of environmental factors on phenotypic variation. An important mediator of developmental plasticity in many animals is parental care. Here, we examine the consequences of maternal care on offspring after the initial mass provisioning of brood in the small carpenter bee,...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-05903-0
更新日期：2018-08-27 00:00:00
abstract：:Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflam...
journal_title：Nature communications
pub_type： 杂志文章,meta分析
doi：10.1038/s41467-020-18528-z
更新日期：2020-09-23 00:00:00
abstract：:Replicating biological patterns is promising for designing materials with multifaceted properties. Twisted cholesteric liquid crystal patterns are found in the iridescent tessellated cuticles of many insects and a few fruits. Their accurate replication is extremely difficult since discontinuous patterns and colors mus...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-17884-0
更新日期：2020-08-14 00:00:00
abstract：:Diverse entry inhibitors targeting the gp120 subunit of the HIV-1 envelope (Env) trimer have been developed including BMS-626529, also called temsavir, a prodrug version of which is currently in phase III clinical trials. Here we report the characterization of a panel of small-molecule inhibitors including BMS-818251,...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-07851-1
更新日期：2019-01-03 00:00:00
abstract：:Single-nucleotide variants that underlie phenotypic variation can affect chromatin occupancy of transcription factors (TFs). To delineate determinants of in vivo TF binding and chromatin accessibility, we introduce an approach that compares ChIP-seq and DNase-seq data sets from genetically divergent murine erythroid c...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-03082-6
更新日期：2018-02-22 00:00:00
abstract：:Hepatocellular-cholangiocarcinoma (H-ChC) is a rare subtype of liver cancer with clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). To date, molecular mechanisms underlying the co-existence of HCC and iCCA components in a single tumor remain elusive. Here, w...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-03276-y
更新日期：2018-03-01 00:00:00
abstract：:Epitaxy is widely employed to create highly oriented crystalline films. A less appreciated, but nonetheless powerful means of creating such films is via topotactic transformation, in which a chemical reaction transforms a single crystal of one phase into a single crystal of a different phase, which inherits its orient...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms8716
更新日期：2015-07-16 00:00:00
