ON THE COVER
A painting by Sam Khalouei entitled “Nuclear Organization” that highlights some of the major aspects of nuclear organization, such as the nuclear pore complex and speckles and the techniques used to visualize them. This painting and the image from Izabela Kaminksi on the following page won the JCB cover contest for this issue on the concept of nuclear organization.
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People & Ideas
McNulty and Sullivan preview work from the Fukagawa laboratory revealing 3D interactions between neocentromeres and distant heterochromatin-rich regions.
Benoit and Poüs highlight new work from Lindeboom et al. revealing how CLASP reorients microtubule networks in plants growing toward light.
Vermunt et al. discuss the relationship between gene-regulatory elements and nuclear architectural features in transcription.
Maass et al. review interchromosomal interactions, which, like intrachromosomal interactions, are emerging as important regulators of genome organization and gene expression.
Mendiratta et al. review the interplay between the different regulatory layers that affect the transcription and dynamics of distinct histone H3 variants along the cell cycle.
Di Carlo et al. discuss how the regulation/dysregulation of Polycomb group proteins contributes to hematopoiesis and hematological disorders.
Ladstätter and Tachibana discuss changes in DNA methylation, chromatin accessibility, and topological architecture occurring during the reprogramming to totipotency in the early embryo.
Schroeder et al. quantitatively evaluate ER architecture in live cells at a ∼50-nm resolution through stimulated emission depletion (STED) microscopy. The ER is not limited to uniform sheets and tubules; they observe dynamic, nanoscale-size holes in ER sheets termed “nanoholes,” and they characterize the effects of perturbations of reticulons, Climp63, and the microtubule cytoskeleton on ER membrane nanostructures.
Wang et al. demonstrate that the novel Bin-Amphiphysin-Rvs (BAR) domain protein FAM92A1 possesses membrane-remodeling activity essential for mitochondrial ultrastructure. The findings uncover a role for BAR domain protein as a critical organizer of the mitochondrial inner membrane that is indispensable for mitochondrial function.
Chakrabarty et al. propose a model in which slow axonal transport of actin can occur by a biased polymerization of actin filaments along the axon shaft without the involvement of microtubules (MTs) or MT-based motors. These dynamics are distinct from polymer sliding—the canonical mechanism thought to convey cytoskeletal cargoes in slow transport.
Neuronal morphology is maintained over long animal lifespans. Noblett et al. show that in Caenorhabditis elegans, DIP-2 acts to inhibit neurite outgrowth during aging and after axotomy, indicating that the maintenance of neuronal morphology and inhibition of axon regeneration may share a common mechanism.
Although centromeres usually associate with heterochromatic repetitive sequences, such repetitive sequences are not detected around neocentromeres. Nishimura et al. performed systematic 4C analysis of cells containing differently positioned neocentromeres and demonstrate that these neocentromeres commonly associate with distant heterochromatin-rich regions at the 3D level.
Events of cytokinesis occur in a precise sequence. Brace et al. describe a checkpoint mechanism in budding yeast that enforces this order by blocking a final secretion event until early division processes are complete.
In Saccharomyces cerevisiae, polarization of Cdc42 is regulated by the cell cycle, but the regulatory mechanisms are not well understood. Moran et al. show that G1 cyclin–dependent kinase activity enables localization of a subset of Cdc42 effectors to sites enriched for Cdc42.
CLASP stabilization of plus ends created by severing promotes microtubule creation and reorientation
During the phototropic response, plant cells reorient their cortical microtubule arrays by generating many new growing microtubules through severing. This study shows how new plus ends created by severing, which lack GTP-caps, are stabilized by CLASP to allow for microtubule amplification and array reorientation.
Purkinje cells rapidly degenerate in pcd mice due to loss of function of tubulin deglutamylase cytosolic carboxypeptidase 1 (CCP1), which promotes mitochondrial fusion in a Drosophila model, CCP1 null cells, and pcd neurons. The CCP1-mediated increase in mitochondrial motility accounts for CCP1-dependent mitochondrial fusion, underscoring the linkage between regulation of mitochondria dynamics, mitochondria motility, and Purkinje neuron survival.
Olenick et al. find that in hippocampal neurons, the cytoplasmic dynein activator Hook1 specifically activates retrograde transport of BDNF–TrkB-signaling endosomes but is not required for motility of other retrograde cargo, supporting a model of cargo-specific effectors for efficient regulation of dynein.
Rsp5 Ubiquitin ligase–mediated quality control system clears membrane proteins mistargeted to the vacuole membrane
Sardana et al. show that protein quality control systems on multiple endocytic organelles cooperate to prevent aberrant protein accumulation and maintain proteostasis. By mistargeting PM proteins de novo to the yeast vacuolar membrane, they uncover a “fail-safe” mechanism that ensures degradation of diverse endocytic cargos.
The actin regulator JMY creates filament networks that move membranes during autophagy. Hu and Mullins find that JMY is normally inhibited by interaction with the STRAP protein, but upon starvation, JMY is recruited away from STRAP and activated by LC3.
Mutations in ATP13A2 cause Kufor-Rakeb syndrome, an atypical form of Parkinson’s disease. Wang et al. characterize the phenotypes of ATP13A2-deficient animals and cells and show that ATP13A2 recruits HDAC6 to lysosomes to deacetylate cortactin, modulating autophagosome–lysosome fusion and autophagy.
HGF-induced migration depends on the PI(3,4,5)P3-binding microexon-spliced variant of the Arf6 exchange factor cytohesin-1
Splice variants of the Arf6 guanine exchange factor cytohesin-1 display differential affinity for PI(4,5)P2 and PI(3,4,5)P3. Ratcliffe et al. show that the specific lipid binding of the diglycine variant of cytohesin-1 is needed for HGF-dependent cell migration and establishment of the leading edge, thereby regulating cancer cell migration following activation of the proto-oncogenic receptor tyrosine kinase Met.
This work describes a role for endothelial N-cadherin in the regulation of endothelial permeability in the brain and lung. N-cadherin adhesions formed between endothelial cells and pericytes increase the abundance of VE-cadherin at adherens junctions through the RhoGEF Trio-dependent activation of RhoA and Rac1.
Tumor cells utilize invadopodia to remodel the surrounding stroma during metastatic invasion. Qiang et al. demonstrate that MTCBP-1 significantly attenuates invadopodia formation and function by binding MT1-MMP and preventing the interaction of MT1-MMP with the actin cytoskeleton.
Tissue injury can lead to fibrotic disease and chronic inflammation, for example, in the lungs of patients with idiopathic pulmonary fibrosis. Jürgensen et al. report that fibroblasts regulate immune responses during tissue injury by clearing collectins with pro- or antiinflammatory activity via uPARAP, an endocytic collectin receptor identified in this work.
To better understand Rho GTPase signaling in neurite outgrowth, Bagonis et al. overcome persisting algorithmic limitations that have, thus far, stymied comprehensive studies of morphological variation among growth cones. They introduce Growth Cone Analyzer—a versatile computer vision tool for the quantification of filopodia-rich cell morphologies.