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Issues

ISSN 0021-9525
EISSN 1540-8140
In this Issue

Spotlights

Sánchez-Martín and Komatsu preview work from Itakura and colleagues that describes a mechanism that mediates degradation of misfolded extracellular proteins.

Drin highlights works from Pemberton et al. and Zewe et al. describing new tools to visualize PI inside cells and clarify how polyphosphoinositides are generated.

Review

Mast et al. review peroxisome biogenesis, interorganellar contacts, and the connections and shared molecular players acting in the formation of peroxisomes and lipid droplets at the ER.

Report

The spindle assembly checkpoint requires recruitment of Mad1-C-Mad2 to unattached kinetochores but also Mad1 binding to Megator/Tpr at nuclear pore complexes during interphase. Cunha-Silva et al. provide evidence that this spatiotemporal redistribution is due to Mps1-mediated dissociation of Mad1 from Megator/Tpr during prophase, which is critical for Mad1-C-Mad2 accumulation at unattached kinetochores and for the accuracy of chromosome segregation in vivo.

Articles

Broad et al. investigate multiple populations of Aurora B kinase at the centromere and kinetochore. Two distinct histone modifications initiate pathways that individually recruit Aurora B to spatially distinct centromeric regions, and neither pathway is required for localization or activity of Aurora B at kinetochores.

Hadders et al. demonstrate that the kinases Haspin and Bub1 recruit separate pools of Aurora B to centromeres of human cells. Surprisingly, the Haspin- and Bub1-dependent pools of Aurora B do not control phosphorylation of important kinetochore substrates nor the mitotic checkpoint.

Viol et al. show that the conserved Never-in-mitosis-A–related kinase-2 (Nek2) removes distal appendage components from the mother centriole prior to mitosis in every cell cycle. These findings suggest that Nek2 prevents cilia maintenance during mitosis via distal appendage regulation.

Nup188 is part of the nuclear pore complex scaffold that is specifically required for heart development. As shown by Vishnoi et al., Nup188 also moonlights as a centrosome protein by binding directly to Cep152 and contributing to centriole duplication.

Cells dividing with late-segregating acentric chromosomes must reincorporate acentrics into telophase daughter nuclei to maintain euploidy. Here, Warecki et al. show that fusion between membrane on acentrics and membrane on daughter nuclei allows acentric passage through channels formed in all components of the nascent nuclear envelope, thus preserving genomic integrity.

Nucleus centering in mouse oocytes depends on a gradient of actin-positive vesicle persistence. Modeling coupled to 3D simulations and experimental testing of predictions coming from the simulations demonstrate that this gradient nonspecifically centers large objects during prophase I and meiosis I in oocytes.

To ensure proper cell growth, the rates of proliferation and protein synthesis are tightly coupled. Haneke et al. demonstrate that the mitotic kinase CDK1 acts as an activator of global protein synthesis during all phases of the cell cycle.

The authors show the dual regulation of phagosomal degradation and migration of Drosophila macrophages by Trpml, a lysosomal calcium channel. Trpml promotes cell migration by activating actomyosin contractility but supports phagosomal degradation through a myosin-independent mechanism.

Coat disassembly, driven by the Hsc70 “uncoating ATPase” and mediated by auxilin, occurs within seconds after vesicle release. Using single-molecule imaging, He et al. find that auxilins are absent from assembling pits. Therefore, Hsc70 is not responsible for the clathrin exchange during pit formation.

Yang et al. demonstrated TORC1 inactivation not only up-regulates macroautophagy and vacuole recycling but also leads to the degradation of many vacuole membrane proteins. The degradation is initiated by ubiquitination and followed by ESCRT-dependent microautophagy. Furthermore, TORC1 directly regulates the activity of vacuole ubiquitination machinery.

ALIX recruits ESCRT-III onto endosomes in a process that does not depend on other ESCRTs but requires the late endosome–specific lipid LBPA in vivo and in vitro. This novel pathway of ILV formation promotes tetraspanin sorting and delivery to exosomes.

Ma et al. describe a novel retrograde trafficking pathway in which type II PI 4-kinase (PI4KII), Past1/EHD1, and Syntaxin-16 are needed for accumulation of PI4P on regulated secretory granules and for the tetraspanin CD63 to promote granule maturation.

Microridges, elongated 3D protrusions arranged in maze-like patterns on zebrafish skin cells, form by the accretion of simple precursor projections. Modeling and in vivo experiments showed that cortical contractions promote the coalescence of precursors into microridges by reducing surface tension.

Local mRNA translation in neurons at a distance from the nucleus is key to new synapse formation. Titlow et al. find that the Syncrip RNA binding protein acts directly on msp300 mRNA to modulate activity-dependent synaptic plasticity. Single-molecule imaging reveals an activity-dependent increase in mRNP complex size and colocalization with ribosomes and the translation initiation factor eIF4E at the synapse.

Itakura et al. identify a protein quality control system for aberrant extracellular proteins, including misfolded proteins and amyloid β. This extracellular proteostasis pathway involves the cell-surface heparan sulfate receptor, which mediates internalization of aberrant extracellular proteins in complex with an extracellular chaperone.

Tools

Schormann et al. provide a reference library of confocal micrographs of key organelles in live epithelial cells as landmarks and a derived feature set that can be used to assign protein localization throughout the secretory pathway and to key organelles via a quantitative unbiased image-based classifier.

Tei et al. developed optogenetic phospholipase D enzymes for precisely generating the pleiotropic lipid second-messenger phosphatidic acid on specific organelle membranes and applied these tools to elucidate that a PM pool of phosphatidic acid can attenuate Hippo signaling.

Zewe et al. develop approaches to map the subcellular distribution of the major phospholipid, phosphatidylinositol (PI), revealing that the lipid is present in most membranes except for plasma membrane, where it is found mainly as PI4P and PI(4,5)P2.

Pemberton et al. characterize a molecular toolbox for the visualization and manipulation of phosphatidylinositol (PI) within intact cells. Results using these approaches define the steady-state distribution of PI across subcellular membrane compartments and provide new insights into the relationship between PI availability and polyphosphoinositide turnover.

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