Abstract:
:In most vertebrate neurons, action potentials are triggered at the distal end of the axon initial segment (AIS). Both position and length of the AIS vary across and within neuron types, with activity, development and pathology. What is the impact of AIS geometry on excitability? Direct empirical assessment has proven difficult because of the many potential confounding factors. Here, we carried a principled theoretical analysis to answer this question. We provide a simple formula relating AIS geometry and sodium conductance density to the somatic voltage threshold. A distal shift of the AIS normally produces a (modest) increase in excitability, but we explain how this pattern can reverse if a hyperpolarizing current is present at the AIS, due to resistive coupling with the soma. This work provides a theoretical tool to assess the significance of structural AIS plasticity for electrical function.
journal_name
Elifejournal_title
eLifeauthors
Goethals S,Brette Rdoi
10.7554/eLife.53432subject
Has Abstractpub_date
2020-03-30 00:00:00issn
2050-084Xpii
53432journal_volume
9pub_type
杂志文章相关文献
eLife文献大全abstract::The integration of cellular and molecular structural data is key to understanding the function of macromolecular assemblies and complexes in their in vivo context. Here we report on the outcomes of a workshop that discussed how to integrate structural data from a range of public archives. The workshop identified two m...
journal_title:eLife
pub_type:
doi:10.7554/eLife.25835
更新日期:2017-07-06 00:00:00
abstract::Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support the tooth, and microbiome dysbiosis. Currently, there is no therapy for reversing periodontal disease, and treatment is generally restricted to preventive mea...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.54318
更新日期:2020-04-28 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::The knirps (kni) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila. Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Pheno...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30281
更新日期:2017-12-23 00:00:00
abstract::The TP53 tumor-suppressor gene is mutated in >50% of human tumors and Li-Fraumeni patients with germ line inactivation are predisposed to developing cancer. Here, we generated tp53 deleted zebrafish that spontaneously develop malignant peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an aggressive ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.37202
更新日期:2018-09-07 00:00:00
abstract::A small molecule called Sm4 can disrupt interactions involving a transcription factor called Sox18, while having little impact on other members of the SoxF family. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.24238
更新日期:2017-01-31 00:00:00
abstract::To improve chemical cross-linking of proteins coupled with mass spectrometry (CXMS), we developed a lysine-targeted enrichable cross-linker containing a biotin tag for affinity purification, a chemical cleavage site to separate cross-linked peptides away from biotin after enrichment, and a spacer arm that can be label...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.12509
更新日期:2016-03-08 00:00:00
abstract::Phosphorylation of eIF2α controls translation initiation by restricting the levels of active eIF2-GTP/Met-tRNAi ternary complexes (TC). This modulates the expression of all eukaryotic mRNAs and contributes to the cellular integrated stress response. Key to controlling the activity of eIF2 are translation factors eIF2B...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.24542
更新日期:2017-03-18 00:00:00
abstract::Motor cortex (M1) has lateralized outputs, yet neurons can be active during movements of either arm. What is the nature and role of activity across the two hemispheres? We recorded muscles and neurons bilaterally while monkeys cycled with each arm. Most neurons were active during movement of either arm. Responses were...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46159
更新日期:2019-10-09 00:00:00
abstract::Actin has well established functions in cellular morphogenesis. However, it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium, in particular when cells have to respond to acute signals. Here, we characterize a rapid and transient actin reset in response to increased in...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.19850
更新日期:2016-12-06 00:00:00
abstract::Telomeres are nucleoprotein complexes at the ends of chromosomes and are indispensable for the protection and lengthening of terminal DNA. Despite the evolutionarily conserved roles of telomeres, the telomeric double-strand DNA (dsDNA)-binding proteins have evolved rapidly. Here, we identified double-strand telomeric ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.64104
更新日期:2021-01-21 00:00:00
abstract::We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were foun...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.15175
更新日期:2016-07-15 00:00:00
abstract::While specific mutations allow organisms to adapt to stressful environments, most changes in an organism's DNA negatively impact fitness. The mutation rate is therefore strictly regulated and often considered a slowly-evolving parameter. In contrast, we demonstrate an unexpected flexibility in cellular mutation rates ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.22939
更新日期:2017-05-02 00:00:00
abstract::The integration of direct bottom-up inputs with contextual information is a core feature of neocortical circuits. In area V1, neurons may reduce their firing rates when their receptive field input can be predicted by spatial context. Gamma-synchronized (30-80 Hz) firing may provide a complementary signal to rates, ref...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.42101
更新日期:2019-02-04 00:00:00
abstract::Learning more about the cells that enable parasitic worms called schistosomes to reproduce inside snails could lead to new treatments that prevent these parasites from being transmitted to humans. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.01115
更新日期:2013-07-30 00:00:00
abstract::In Drosophila larvae, Class IV sensory neurons respond to noxious thermal stimuli and provoke heat avoidance behavior. Previously, we showed that the activated neurons displayed characteristic fluctuations of firing rates, which consisted of repetitive high-frequency spike trains and subsequent pause periods, and we p...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.29754
更新日期:2017-10-16 00:00:00
abstract::Unfolded protein responses (UPRs) safeguard cellular function during proteotoxic stress and aging. In a previous paper (Lehrbach and Ruvkun, 2016) we showed that the ER-associated SKN-1A/Nrf1 transcription factor activates proteasome subunit expression in response to proteasome dysfunction, but it was not established ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44425
更新日期:2019-04-11 00:00:00
abstract:: ...
journal_title:eLife
pub_type: 已发布勘误
doi:10.7554/eLife.65214
更新日期:2020-12-04 00:00:00
abstract::Multi-modal MRI techniques have identified biomarkers that could help to predict whether someone will develop epilepsy. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.29853
更新日期:2017-07-26 00:00:00
abstract::Social rank differentially influences how male and female mice respond to chronic stress. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.63996
更新日期:2020-11-20 00:00:00
abstract::Numerous links exist between co-transcriptional RNA processing and the transcribing RNAPII. In particular, pre-mRNA splicing was reported to be associated with slowed RNAPII elongation. Here, we identify a site of ubiquitination (K1246) in the catalytic subunit of RNAPII close to the DNA entry path. Ubiquitination was...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.27082
更新日期:2017-10-13 00:00:00
abstract::Apical secretion from epithelial tubes of the Drosophila embryo is mediated by apical F-actin cables generated by the formin-family protein Diaphanous (Dia). Apical localization and activity of Dia are at the core of restricting F-actin formation to the correct membrane domain. Here we identify the mechanisms that tar...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.00666
更新日期:2013-07-09 00:00:00
abstract::The characteristics of goal-directed actions tend to resemble those of previously executed actions, but it is unclear whether such effects depend strictly on action history, or also reflect context-dependent processes related to predictive motor planning. Here we manipulated the time available to initiate movements af...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.26713
更新日期:2017-10-23 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::Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.11288
更新日期:2016-03-17 00:00:00
abstract::Although seasonality is widespread and can cause fluctuations in the intensity and direction of natural selection, we have little information about the consequences of seasonal fitness trade-offs for population dynamics. Here we exposed populations of Drosophila melanogaster to repeated seasonal changes in resources a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.18770
更新日期:2017-02-06 00:00:00
abstract::IRE1α is an endoplasmic reticulum (ER) localized endonuclease activated by misfolded proteins in the ER. Previously, we demonstrated that IRE1α forms a complex with the Sec61 translocon, to which its substrate XBP1u mRNA is recruited for cleavage during ER stress (Plumb et al., 2015). Here, we probe IRE1α complexes in...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.27187
更新日期:2017-05-15 00:00:00
abstract::Plasma cells (PCs) are essential for protection from infection, and at the origin of incurable cancers. Current studies do not circumvent the limitations of removing PCs from their microenvironment and confound formation and maintenance. Also, the investigation of PC population dynamics has mostly relied on nucleotide...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.59850
更新日期:2020-11-02 00:00:00
abstract::Intrinsically disordered proteins (IDPs) present a functional paradox because they lack stable tertiary structure, but nonetheless play a central role in signaling, utilizing a process known as allostery. Historically, allostery in structured proteins has been interpreted in terms of propagated structural changes that...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30688
更新日期:2017-10-12 00:00:00
abstract::Hippo signalling integrates diverse stimuli related to epithelial architecture to regulate tissue growth and cell fate decisions. The Hippo kinase cascade represses the growth-promoting transcription co-activator Yorkie. The FERM protein Expanded is one of the main upstream Hippo signalling regulators in Drosophila as...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46592
更新日期:2019-09-30 00:00:00