Abstract:
:A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is thought to function as an injury 'sensor', as it becomes activated after axonal damage. Our findings in both Drosophila and mammalian neurons indicate that the cAMP effector kinase PKA is a conserved and direct upstream activator of Wnd/DLK. PKA is required for the induction of Wnd signaling in injured axons, and DLK is essential for the regenerative effects of cAMP in mammalian DRG neurons. These findings link two important mediators of responses to axonal injury, DLK/Wnd and cAMP/PKA, into a unified and evolutionarily conserved molecular pathway for stimulating the regenerative potential of injured axons.
journal_name
Elifejournal_title
eLifeauthors
Hao Y,Frey E,Yoon C,Wong H,Nestorovski D,Holzman LB,Giger RJ,DiAntonio A,Collins Cdoi
10.7554/eLife.14048subject
Has Abstractpub_date
2016-06-07 00:00:00issn
2050-084Xjournal_volume
5pub_type
杂志文章相关文献
eLife文献大全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::Intergroup conflict contributes to human discrimination and violence, but persists because individuals make costly contributions to their group's fighting capacity. Yet, how group members effectively coordinate their contributions during intergroup conflict remains poorly understood. Here, we examine the role of oxyto...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.40698
更新日期:2019-01-25 00:00:00
abstract::The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed 'Opto-CRAC') that selectively ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.10024
更新日期:2015-12-08 00:00:00
abstract::After paralyzing spinal cord injury the adult nervous system has little ability to 'heal' spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weig...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.23532
更新日期:2017-06-29 00:00:00
abstract::Though neurotransmitters are essential elements in neuronal signal transduction, techniques for in vivo analysis are still limited. Here, we describe an organic electrochemical transistor array (OECT-array) technique for monitoring catecholamine neurotransmitters (CA-NTs) in rat brains. The OECT-array is an active sen...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.50345
更新日期:2020-02-11 00:00:00
abstract::Acquisition of pluripotency is driven largely at the transcriptional level by activators OCT4, SOX2, and NANOG that must in turn cooperate with diverse coactivators to execute stem cell-specific gene expression programs. Using a biochemically defined in vitro transcription system that mediates OCT4/SOX2 and coactivato...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03573
更新日期:2014-11-19 00:00:00
abstract::Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03781
更新日期:2014-09-12 00:00:00
abstract::Yes. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.40018
更新日期:2018-07-23 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::Cells and organelles are not homogeneous but include microcompartments that alter the spatiotemporal characteristics of cellular processes. The effects of microcompartmentation on metabolic pathways are however difficult to study experimentally. The pyrenoid is a microcompartment that is essential for a carbon concent...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.37960
更新日期:2018-10-11 00:00:00
abstract::Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that interact trans-synaptically with neurexins to mediate synapse development and function. NLGN2 is only at inhibitory synapses while NLGN3 is at both excitatory and inhibitory synapses. We found that NLGN3 function at inhibitory synapses in rat CA1 depend...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.19236
更新日期:2016-11-02 00:00:00
abstract::The transcription factor TCF7L1 is an embryonic stem cell signature gene that is upregulated in multiple aggressive cancer types, but its role in skin tumorigenesis has not yet been defined. Here we document TCF7L1 upregulation in skin squamous cell carcinoma (SCC) and demonstrate that TCF7L1 overexpression increases ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.23242
更新日期:2017-05-03 00:00:00
abstract::Previously, we found that in the mammalian retina, inhibitory inputs onto starburst amacrine cells (SACs) are required for robust direction selectivity of On-Off direction-selective ganglion cells (On-Off DSGCs) against noisy backgrounds (Chen et al., 2016). However, the source of the inhibitory inputs to SACs and how...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.62618
更新日期:2020-12-03 00:00:00
abstract::Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exh...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04494
更新日期:2015-01-20 00:00:00
abstract::The biological players involved in angiogenesis are only partially defined. Here, we report that endothelial cells (ECs) express a novel isoform of the cell-surface adhesion molecule L1CAM, termed L1-ΔTM. The splicing factor NOVA2, which binds directly to L1CAM pre-mRNA, is necessary and sufficient for the skipping of...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44305
更新日期:2019-03-04 00:00:00
abstract::Prion diseases are caused by PrPSc, a self-replicating pathologically misfolded protein that exerts toxicity predominantly in the brain. The administration of PrPSc causes a robust, reproducible and specific disease manifestation. Here, we have applied a combination of translating ribosome affinity purification and ri...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.62911
更新日期:2020-09-22 00:00:00
abstract::SynGAP is a postsynaptic density (PSD) protein that binds to PDZ domains of the scaffold protein PSD-95. We previously reported that heterozygous deletion of Syngap1 in mice is correlated with increased steady-state levels of other key PSD proteins that bind PSD-95, although the level of PSD-95 remains constant (Walku...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.52656
更新日期:2020-01-15 00:00:00
abstract::Spatial and temporal cues are required to specify neuronal diversity, but how these cues are integrated in neural progenitors remains unknown. Drosophila progenitors (neuroblasts) are a good model: they are individually identifiable with relevant spatial and temporal transcription factors known. Here we test whether s...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44036
更新日期:2019-01-29 00:00:00
abstract::C-type inactivation of potassium channels fine-tunes the electrical signaling in excitable cells through an internal timing mechanism that is mediated by a hydrogen bond network in the channels' selectively filter. Previously, we used nonsense suppression to highlight the role of the conserved Trp434-Asp447 indole hyd...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.18976
更新日期:2016-10-06 00:00:00
abstract::The integrity of the nuclear membranes coupled to the selective barrier of nuclear pore complexes (NPCs) are essential for the segregation of nucleoplasm and cytoplasm. Mechanical membrane disruption or perturbation to NPC assembly triggers an ESCRT-dependent surveillance system that seals nuclear pores: how these por...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45284
更新日期:2019-04-03 00:00:00
abstract::The Cdc45/Mcm2-7/GINS (CMG) helicase separates DNA strands during replication in eukaryotes. How the CMG is assembled and engages DNA substrates remains unclear. Using electron microscopy, we have determined the structure of the CMG in the presence of ATPγS and a DNA duplex bearing a 3' single-stranded tail. The struc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03273
更新日期:2014-08-12 00:00:00
abstract::Cavin-3 regulates metabolism and cell proliferation by coordinating the activities of growth factor signalling cascades. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.01428
更新日期:2013-09-24 00:00:00
abstract::Signaling molecules activate distinct patterns of gene expression to coordinate embryogenesis, but how spatiotemporal expression diversity is generated is an open question. In zebrafish, a BMP signaling gradient patterns the dorsal-ventral axis. We systematically identified target genes responding to BMP and found tha...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.58641
更新日期:2020-11-11 00:00:00
abstract::Dendritic spines are specialized postsynaptic structures that transduce presynaptic signals, are regulated by neural activity and correlated with learning and memory. Most studies of spine function have focused on the mammalian nervous system. However, spine-like protrusions have been reported in C. elegans (Philbrook...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47918
更新日期:2019-10-04 00:00:00
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::Translation is a core cellular process carried out by a highly conserved macromolecular machine, the ribosome. There has been remarkable evolutionary adaptation of this machine through the addition of eukaryote-specific ribosomal proteins whose individual effects on ribosome function are largely unknown. Here we show ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.11154
更新日期:2016-04-27 00:00:00
abstract::The link between the combined action of neuromodulators in the brain and global brain states remains a mystery. In this study, using biophysically realistic models of the thalamocortical network, we identified the critical intrinsic and synaptic mechanisms, associated with the putative action of acetylcholine (ACh), G...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.18607
更新日期:2016-11-16 00:00:00
abstract::Direct reprogramming of fibroblasts to neurons induces widespread cellular and transcriptional reconfiguration. Here, we characterized global epigenomic changes during the direct reprogramming of mouse fibroblasts to neurons using whole-genome base-resolution DNA methylation (mC) sequencing. We found that the pioneer ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.40197
更新日期:2019-01-15 00:00:00
abstract::Ribonucleotide reductases (RNRs) convert ribonucleotides into deoxyribonucleotides, a reaction essential for DNA replication and repair. Human RNR requires two subunits for activity, the α subunit contains the active site, and the β subunit houses the radical cofactor. Here, we present a 3.3-Å resolution structure by ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.31502
更新日期:2018-02-20 00:00:00
abstract::Cell surface reception of Sonic hedgehog (Shh) must ensure that the graded morphogenic signal is interpreted accordingly in neighboring cells to specify tissue patterns during development. Here, we report endocytic sorting signals for the receptor Patched1 (Ptch1), comprising two 'PPXY' motifs, that direct it to degra...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02555
更新日期:2014-06-12 00:00:00