ON THE COVER
The epidermal–dermal interface of murine skin is visualized by two-photon imaging of epidermal cells (tdTomato), the nuclei of epidermal cells (H2BGFP), and collagen fibers (gray). Mammalian skin is an ideal system to study microRNA functions such as how the miR-200 family controls skin development.
Image © Hoefert et al., 2018.
See page 2185.
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People & Ideas
Takahashi and Hirota preview work from Stanyte et al. examining the behavior of sister chromatids and their resolution as the cell cycle progresses.
Brayson et al. preview work from Wong et al. that provides evidence supporting the hypothesis that cell and tissue mechanics play a crucial role in the regulation of key nuclear functions.
Smith and Scott discuss work from Isensee et al. addressing the long-standing question of the regulation of protein kinase A–II activity by phosphorylation.
Wang et al. introduce new work from Chang et al. revealing the function of STIM1 binding by EB1 in SOCE.
Yoon et al. review epigenetic and epitranscriptomic mechanisms that regulate the lineage specification of neural progenitor cells in the developing brain.
Wang et al. review the dual role of superoxide dismutases in controlling reactive oxygen species (ROS) damage and regulating ROS signaling across model systems as well as their involvement in human diseases.
Through two superresolution microscopy techniques, STED and STORM, Spiess et al. visualize the organization of integrins in focal adhesions and show that active and inactive β1 integrins assemble into distinct nanoclusters within adhesions, suggesting the existence of a novel mechanism that locally coordinates integrin activity.
Multiciliated cells (MCCs) function to promote directional fluid flow across epithelial tissues. Wang et al. show that TRRAP, a component of multiple histone acetyltransferase complexes, is required for airway MCC formation and regulates a network of genes involved in MCC differentiation and function.
Centromere transcription allows CENP-A to transit from chromatin association to stable incorporation
How transcription contributes to the loading of the centromere histone CENP-A is unclear. Bobkov et al. report that transcription-mediated chromatin remodeling enables the transition of centromeric CENP-A from chromatin association to full nucleosome incorporation.
Combining fluorescence labeling with live-cell confocal and correlative super-resolution microscopy, Xiang et al. characterize biophysical parameters defining the internal organization, spacing, and mechanical coupling of replication domains.
Stanyte et al. use dCas9-mEGFP labelling to image endogenous genomic loci and show that sister loci separate shortly after their replication and rapidly equilibrate their relative position, thereby establishing a sister chromatid resolution topology in G2 that largely reflects the DNA replication program. The data suggest that cohesin enrichment sites are not persistent cohesive sites in human cells.
Nuclear mechanotransduction has been implicated in the control of chromatin organization and gene expression. Wang et al. show that, in Drosophila myofibers, the LINC complex is required for the regulation of DNA replication and synchronized cell-cycle progression in myonuclei.
Quality control (QC) pathways for misfolded proteins depend on E3 ubiquitin ligases and associated chaperones. Prasad et al. show that Hsp40/70/110 chaperones traffic and manage misfolded proteins in the nucleus, extending the nuclear protein QC pathway to include cytosolic clients.
Single-headed myosin 1 proteins are known to be expressed in neurons, but their function in these cells is still unclear. Iuliano et al. show that myosin 1b plays a major role in neuronal symmetry breaking via modulation of growth cone actin distribution and the propagation of actin waves.
EB1 binding restricts STIM1 translocation to ER–PM junctions and regulates store-operated Ca2+ entry
STIM1 activates store-operated Ca2+ entry (SOCE) by translocating to endoplasmic reticulum–plasma membrane junctions. Chang et al. reveal that STIM1 localization and SOCE are regulated by a dynamic trapping mechanism mediated by STIM1 binding to EB1 at growing microtubule ends.
Romo1 regulates mitochondrial reactive oxygen species production and acts as an essential redox sensor in mitochondrial dynamics. Lee et al. demonstrate that Romo1 is a unique mitochondrial ion channel with viroporin-like characteristics that distinguish Romo1 from other known eukaryotic ion channels.
SFT-4/Surf4 control ER export of soluble cargo proteins and participate in ER exit site organization
Saegusa et al. report that the SFT-4/Surf4 cargo receptor homologs mediate export of soluble proteins such as lipoproteins from the ER. Efficient export of yolk proteins in C. elegans intestinal cells, or apoliprotein trafficking in human hepatocytes, requires SFT-4/Surf4 so that they may enhance secretion by maintaining ER exit site organization.
Membranes and membrane proteins destined for peroxisomes are trafficked from the endoplasmic reticulum (ER) in preperoxisomal vesicles. Mast et al. define a role for ESCRT-III in releasing these vesicles from the ER.
High levels of autophagy exist in Leydig cells of the testis, but its physiological function is unknown. Gao et al. now show that autophagy promotes uptake of cholesterol, an essential precursor for testosterone synthesis, by removing the NHERF2 negative regulator of the high-density lipoprotein receptor SR-BI.
Arf6/ARF-6 is a crucial regulator of the endosomal PI(4,5)P2 pool in endocytic recycling. Chen et al. show that SAC-1 is important for epithelial cell recycling in C. elegans. SAC-1 acts as a novel interactor for ARF-6, curbing ARF-6 activity by limiting the access of ARF-6(GDP) to its GEF BRIS-1.
Caveolae are linked to signaling protein regulation through interactions with caveolins. We describe a cell-free system for the biogenesis of caveolae and show phosphorylated-caveolins preferentially bind signaling proteins. Our validation in vivo shows that phosphorylated CAV1 recruits TRAF2 to the endosome to form a signaling platform.
Activity of endogenous protein kinase A (PKA) could never be analyzed directly in the cellular environment. Isensee et al. used antibodies to quantify conformational changes leading to an open conformation of endogenous PKA-II holoenzymes, which allowed them to analyze and model its activation cycle in primary sensory neurons.
The microRNA-200 family coordinately regulates cell adhesion and proliferation in hair morphogenesis
Understanding how multiple micro RNAs (miRNAs) regulate their targets genome-wide holds promise for deciphering complex cellular regulatory networks. In this study, Hoefert et al. use CLEAR-CLIP to dissect miRNA-200 family targeting and reveal a novel role for these miRNAs in regulating cell adhesion and hair follicle morphogenesis.
Inflammation stimulates lymphatic endothelial cells to release exosomes, which accumulate in the perivascular stroma. Brown et al. show that these exosomes promote the directional migration of dendritic cells along guidance cues in complex environments by enhancing dynamic cellular protrusions in a CX3CL1-dependent manner.