The N-terminus of the FGF14b isoform promotes the inactivation of voltage-gated Na+ channels to regulate the resurgent Na+ channel current needed for high frequency action potentials.
Justin M Miller, Buenafe T Arachea ... Eric J Enemark
Building on previous work (Froelich et al., 2014), we present the X-ray crystal structure of an active MCM hexamer, which suggests a mechanism for MCM regulation and demonstrates a key interaction between the major domains.
Signaling by TAM receptor tyrosine kinases requires the coincident engagement of a TAM ligand with both its receptor and the phospholipid phosphatidylserine.
Genomic landmarks, known generically as ‘CpG islands’, program chromatin structure via their richness in the dinucleotide CG and their skewed composition of DNA bases.
Arnaud R Krebs, Sophie Dessus-Babus ... Dirk Schübeler
Large numbers of DNA sequence variants comprehensively define how transcription factor binding sites and CG density preserve mammalian promoters from repression by DNA methylation.
Rigorous assays of membrane fusion show that a distinct tethering step is required for lumenal compartment mixing in a manner that extends beyond simply increasing the amount of total trans-SNARE complex.
Fringe proteins modulate cis inhibitory, same-cell interactions between the Notch receptor and its ligands to control whether, and in which direction, cells can signal to one another.
Joan Isern, Andrés García-García ... Simón Méndez-Ferrer
Developing long bones contain distinct mesenchymal stem-cell populations derived from mesoderm and neural crest, which have specialized functions in skeleton formation and the establishment of the hematopoietic stem-cell niche, respectively.
Jennifer M Kavran, Jacqueline M McCabe ... Daniel J Leahy
Ligand binding to the ectodomain of the insulin-like growth factor receptor destabilises an autoinhibitory inter-subunit interaction, which allows the transmembrane domains to associate and the intracellular regions to autophosphorylate.
Ines A Drinnenberg, Dakota deYoung ... Harmit Singh Malik
CenH3, the defining component of centromeres in almost all eukaryotes, was independently lost in four insect lineages that transitioned from monocentricity to holocentricity.
Whole-genome in silico screening for stop codon contexts that produce elevated translational readthrough and peroxisome targeting reveals that in mammals, the amount of lactate dehydrogenase in the peroxisome is controlled by translational readthrough.
Differentiation-specific maintenance of genome integrity during S-phase is essential for establishing both the structure and function of the cerebral cortex.
Interactions between Neuropilin-1 and VEGFR2, rather than VEGF-Neuropilin-1 binding, underlie Neuropilin-1's critical function in VEGF-mediated vascular development.
A transport mechanism is uncovered in the major drug-efflux system in E. coli involving two remote alternating-access conformational cycles, which could provide the basis for the development of allosteric inhibitors against multidrug resistance.
Transcribed promoters are highly susceptible to mutation by cytidine deaminases, implicating stable exposure of single stranded DNA structures, rather than cofactors, in localising mutation during tumourigenesis and antibody maturation.
Jonathan M Stokes, Joseph H Davis ... Eric D Brown
The anticonvulsant drug lamotrigine inhibits bacterial ribosome biogenesis and reveals an unexplored role for initiation factor 2 (IF2) in ribosome assembly.
Vassilis Bitsikas, Ivan R Corrêa Jr, Benjamin J Nichols
Chemical labelling of all primary endocytic vesicles allows the contribution of different endocytic mechanisms to the total endocytic uptake in cultured mammalian cells to be quantified.
Alexandre Pfister, Marie Barberon ... Niko Geldner
The SCHENGEN3 protein is needed for the progression of isolated microdomains into a continuous band, which is necessary for the establishment of the major extracellular diffusion barrier in plant roots: the Casparian strip.
Eukaryotic translation elongation factor 1A1 controls the process of heat shock response, from transcriptional activation of the HSP70 gene, to HSP70 mRNA stabilization, nuclear export, and translation.
Measuring HIV-1 DNA levels at the time of stopping antiretroviral therapy (when initiated during primary infection) predicts clinical progression and the time taken for plasma viraemia to become detectable.
The pattern of past Ebola outbreaks is indicative of an effective reproductive ratio of less than 1, which can lead to the generation of a range of outbreak sizes consistent with the scale of the ongoing epidemic.
Physical and functional interactions between HNF4A and TAF4 coordinate HNF4A genomic occupancy with pre-initiation complex formation to activate post-natal hepatocyte gene expression.
Joseph Atherton, Irene Farabella ... Carolyn A Moores
Cryo-electron microscopy reconstructions of two microtubule-bound transport kinesins at 7 Å resolution reveal how microtubule track binding stimulates ADP release, primes the active site for ATP binding and enables force generation.
Controlling cell cycle progression in a developing embryo directly depends on de novo histone supply and a specialized surveillance mechanism for nucleosome assembly.
Farzaneh Najafi, Andrea Giovannucci ... Javier F Medina
Sensory-driven calcium spikes in Purkinje cells are not binary; instead, they are graded and can provide information about the strength of a periocular airpuff stimulus known to drive learning.
Understanding where future Ebola virus outbreaks may start and the changing nature of the populations living in these places is of critical importance in helping to prepare for future outbreaks.
The THAP-domain protein Bip1, along with other proteins Nup98 and RpS8, controls the expression of the protein Pvr, a critical non-cell-autonomous regulator of Drosophila blood progenitor maintenance.
Zachary A Knight, Sarah F Schmidt ... Jeffrey M Friedman
Transcription profiling of activated cells using Phospho-Trap, a new method for identifying activated cells, reveals a critical role for mTOR signaling in red blood cell development and the pathogenesis of anemia
Kiersten A Henderson, Adam L Hughes, Daniel E Gottschling
Protons are pumped out of mother cells by a protein that accumulates over time and this leads to cellular aging, but this protein is largely absent from daughter cells, which mediates rejuvenation.
A protein within the nuclear membrane, MAN1, controls the expression of the circadian clock gene, BMAL1, in an example of cross-talk between two major gene regulatory pathways.
Using mice expressing a Bcl-2 mutant protein to suppress multiple central tolerance pathways, it is shown that central tolerance is crucial for preventing autoimmunity.
Debashree Chatterjee, Richard B Cooley ... Holger Sondermann
Structure-function analyses reveal the mechanistic underpinnings of inside-out transmembrane signaling that controls periplasmic proteolysis, and thereby biofilm formation, in bacteria and may be relevant in the context of other signaling proteins with similar control elements.
Giselle Roman-Hernandez, Janine H Peterson, Harris D Bernstein
A complex that catalyzes the membrane integration of β barrel proteins and a molecular chaperone promote the complete assembly of a bacterial virulence factor in vitro.
The theory of Buffered Qualitative Stability uses the importance of biological robustness to explain many features of gene regulatory networks in a wide range of organisms, and has implications for diverse biological phenomena including the ability of bacteria and cancer cells to ‘loosen’ their robustness and hence evade treatment.
Cells within the retina synchronize transmitter release across their output synapses in the dark, reducing the impact of noise generated at these synapses and allowing light-dependent signals to be transmitted with minimal added synaptic noise.