eLife
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Selective agonist of TRPML2 reveals direct role in chemokine release from innate immune cellsCytokines and chemokines are produced and secreted by a broad range of immune cells including macrophages. Remarkably, little is known about how these inflammatory mediators are released from the various immune cells. Here, the endolysosomal cation channel TRPML2 is shown to play a direct role in chemokine trafficking and secretion from murine macrophages. To demonstrate acute and direct i... ...
eLife - Tập 7
Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal functionIon selectivity is a defining feature of a given ion channel and is considered immutable. Here we show that ion selectivity of the lysosomal ion channel TPC2, which is hotly debated (Calcraft et al., 2009; Guo et al., 2017; Jha et al., 2014; Ruas et al., 2015; Wang et al., 2012), depends on the activating ligand. A high-throughput screen identified two structurally distinct TPC2 agonists. ... ...
eLife - Tập 9
2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20S proteasome using cryo-electron microscopyRecent developments in detector hardware and image-processing software have revolutionized single particle cryo-electron microscopy (cryoEM) and led to a wave of near-atomic resolution (typically ∼3.3 Å) reconstructions. Reaching resolutions higher than 3 Å is a prerequisite for structure-based drug design and for cryoEM to become widely interesting to pharmaceutical industries. We report ... ...
eLife - Tập 4
Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neuronsIn this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by sliding antiparallel microtubules. At later stages, the microtubule orientation in the axon ... ...
eLife - Tập 4
Beam-induced motion correction for sub-megadalton cryo-EM particlesIn electron cryo-microscopy (cryo-EM), the electron beam that is used for imaging also causes the sample to move. This motion blurs the images and limits the resolution attainable by single-particle analysis. In a previous Research article (<xref ref-type="bibr" rid="bib3">Bai et al., 2013</xref>) we showed that correcting for this motion by processing movies from fast direct-e... ...
eLife - Tập 3
A cortical disinhibitory circuit for enhancing adult plasticityThe adult brain continues to learn and can recover from injury, but the elements and operation of the neural circuits responsible for this plasticity are not known. In previous work, we have shown that locomotion dramatically enhances neural activity in the visual cortex (V1) of the mouse (<xref ref-type="bibr" rid="bib27">Niell and Stryker, 2010</xref>), identified the cortica... ...
eLife - Tập 4
High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrierDiabetes mellitus is a known susceptibility factor for severe influenza virus infections. However, the mechanisms that underlie this susceptibility remain incompletely understood. Here, the effects of high glucose levels on influenza severity were investigated using an in vitro model of the pulmonary epithelial-endothelial barrier as well as an in vi... ...
eLife - Tập 9
Remyelination alters the pattern of myelin in the cerebral cortexDestruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters neural activity and is associated with cognitive disability in multiple sclerosis (MS). Myelin can be restored by regenerating oligodendrocytes from resident progenitors; however, it is not known whether regeneration restores the complex myelination patterns in cortical circuits. Here, we performed... ...
eLife - Tập 9
Region-specific myelin differences define behavioral consequences of chronic social defeat stress in miceExposure to stress increases the risk of developing mood disorders. While a subset of individuals displays vulnerability to stress, others remain resilient, but the molecular basis for these behavioral differences is not well understood. Using a model of chronic social defeat stress, we identified region-specific differences in myelination between mice that displayed social avoidance behav... ...
eLife - Tập 8
Proteome dynamics during homeostatic scaling in cultured neuronsProtein turnover, the net result of protein synthesis and degradation, enables cells to remodel their proteomes in response to internal and external cues. Previously, we analyzed protein turnover rates in cultured brain cells under basal neuronal activity and found that protein turnover is influenced by subcellular localization, protein function, complex association, cell type of origin, a... ...
eLife - Tập 9
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