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Igaki explores how cell–cell communication directs tissue and tumor development.

Spotlight

Goodwin and Nelson discuss the recent discovery by Sirka et al. that remodeling activity of myoepithelial cells can control breast cancer cell invasion.

Gao and Yang preview studies from Bean et al. and Kumar et al. unveiling the molecular function of VPS13 and how its cellular localization is regulated.

Pai and Moore preview work from Nithianandam and Chien describing new actin structures called blobs that prefigure dendrite branching.

Newman and Shadel preview new work from the Youle laboratory published in Nature indicating that mitophagy mitigates STING-induced inflammation.

Perspective

Lele et al. review sources of cellular forces on the nucleus and the structural contributors to its mechanical response.

Report

Sister chromatid cohesion is a prerequisite for faithful mitosis. Through artificial removal of precise amounts of cohesin from metaphase chromosomes, Carvalhal et al. show that sister chromatid cohesion is highly resistant to cohesin loss. Nevertheless, partial cohesin decay compromises mitotic fidelity by impairing chromosome attachments.

Multiple ER-phagy receptors have been reported recently, but other mediators or regulators have remained elusive. Liang et al. developed two ER-phagy–specific reporter assays and showed that Atlastins, a family of ER surface GTPases, are positive regulators of ER-phagy that act downstream of an ER-phagy receptor, FAM134B.

Myoepithelial cells function collectively as a dynamic barrier to the invasion and dissemination of Twist1+ luminal epithelial cells and both luminal and basal phenotype breast cancer cells. Barrier function depends on myoepithelial abundance and both smooth muscle contractility and intercellular adhesion within the myoepithelium.

Article

The SAGA coactivator complex and the nuclear pore–associated TREX-2 complex couple transcription with mRNA export. Evangelista et al. identify a novel interplay between TREX-2 and the deubiquitination module of SAGA that is necessary to maintain monoubiquitinated H2B levels required for efficient DNA repair through homologous recombination.

The Set1C/COMPASS subunit Spp1 plays an important role in recruiting meiosis double-strand breaks to the chromosome axis to initiate meiotic recombination. Karányi et al. show that Spp1 prepares recombination initiation sites for break formation: Spp1 interacts with the chromosome axis protein Mer2 independently of Set1C, and the association of Spp1 with Mer2 axial sites reduces its turnover and diffusion upon chromatin binding.

Acentrosomal spindle assembly in mouse oocytes depends on chromosomes and acentriolar microtubule-organizing centers (aMTOCs). Manil-Ségalen et al. observe that Plk4-induced perturbation of aMTOCs coupled to Cre-mediated gene editing generates fragile chromosomes that break when subjected to forces exerted by altered meiosis I spindles.

Romé and Ohkura show that the kinesin-6 Subito/MKlp2 mediates a novel oocyte-specific microtubule nucleation pathway, which is essential for assembling spindle microtubules complementarily with the Augmin pathway.

Cdt1 is a novel kinetochore–microtubule binding protein. The middle and the C-terminal winged-helix domains of Cdt1 are involved in microtubule binding. Aurora B kinase phosphorylation of Cdt1 influences its microtubule binding in vitro and is necessary for kinetochore–microtubule stability and mitotic progression in cells.

RBM3 plays a protective role in embryonic neurogenesis. This study finds that maternal cold stress affects the embryonic brain development via RBM3 and Yap. When RBM3 is knocked down or knocked out under the maternal cold stress, the embryonic neurogenesis was impaired.

Uncovering the mechanistic link between kinesin motors and neuropathy, Xu et al. identify functional KIF1Bβ mutations in human hereditary neuropathy to analyze them in mouse models. They propose that KIF1Bβ transports IGF1R and facilitates axonal outgrowth. Both of these effects are significantly affected by the clinical mutations.

Conventional kinesin is essential for Drosophila melanogaster posterior determination by localizing oskar mRNA at the oocyte posterior pole. In this study, we show that two essential kinesin functions, cargo transport and cytoplasmic streaming, together with a myosin V–mediated cortical anchorage ensure correct posterior determination.

This study shows that in vivo actin nucleation by the yeast formin Bnr1 is controlled through the coordinated effects of two distinct regulators, a stationary inhibitor (the F-BAR protein Hof1) and a mobile activator (Bud6), establishing a positive feedback loop for precise spatial and temporal control of actin assembly.

How the actin and microtubule cytoskeletons work together during diverse cellular functions is unclear. Wu et al. describe an apical actin pool in plant cells organized by a microtubule template at the site of polarized growth. Disconnecting the two cytoskeletons by removing class VIII myosins alters both cytoskeletal structures and impairs polarized growth.

Although human papillomaviruses (HPVs) cause many human cancers, the cellular basis of HPV infection remains mysterious. This manuscript reveals that the transmembrane protease γ-secretase harbors a novel chaperone activity, promoting insertion of the HPV L2 protein into endosomal membranes. L2 membrane insertion is required for further progression of infection.

In Special Collection:
Lipid and membrane biology 2019

Cellular lipid metabolism is being increasingly recognized to influence inflammatory responses. de la Roche et al. reveal that cellular sterol trafficking to the endoplasmic reticulum is required for the assembly and the activation of the NLRP3 inflammasome, thereby coupling lipid homeostasis to innate immune signaling.

Endoplasmic reticulum (ER) morphology is dynamic and key to its function during different cellular processes. Dong et al. now show in convergent studies in human cells and Caenorhabditis elegans neurons that a phosphoinositide phosphatase (INPP5K) is localized on the surface of the ER network and helps control the shape of the ER.

Targeting of Vps13 to membranes is highly dynamic. Bean et al. identify Ypt35 and Mcp1 as adaptors for Vps13 at endosomes and mitochondria, respectively, and show all known Vps13 adaptors use a related motif to compete for Vps13 membrane recruitment.

How specific dynamin-related proteins (DRPs) are tailored to their cellular targets is an open question. Varlakhanova et al. present structures of the fungal DRP Vps1, which functions at the endosomal compartment. The crystal and cryoEM structures reveal a unique DRP architecture that highlights structural flexibilities of DRP self-assembly.

Structural and biochemical studies show that VPS13 family proteins are lipid transporters. VPS13A and VPS13C tether the ER to mitochondria and to endosomes/lysosomes, respectively, suggesting lipid dyshomeostasis as the cause of chorea acanthocytosis and Parkinson’s disease resulting from their mutations.

In Special Collection:
Autophagy 2019 , JCB65: Autophagy

Mejlvang et al. show that amino acid starvation of human fibroblasts and a lung cancer cell line induces a rapid and selective degradation of a subset of proteins, including autophagy receptors p62/SQSTM1, NBR1, TAX1BP1, NDP52, and NCOA4, that is independent from mTOR and canonical macroautophagy but dependent on endosomal microautophagy.

Autophagosome fusion with vacuoles requires a conserved fusion machinery, though the topology remained unclear. Two papers in this issue, Bas et al. and Gao et al., uncover Ykt6 as the required autophagosomal SNARE.

In Special Collection:
Autophagy 2019

Autophagosome fusion with vacuoles requires a conserved fusion machinery, though the topology remained unclear. Two papers in this issue, Bas et al. and Gao et al., uncover Ykt6 as the required autophagosomal SNARE.

Hutchins and Bronner show that a transient pulse of the secreted molecule Draxin regulates the timing and progression of cranial neural crest EMT along the anterior to posterior embryonic body axis by modulation of canonical Wnt signaling.

Phosphorylation by protein kinase GSK3-β is essential for desmin filament depolymerization by calpain-1 and the resulting myofibril destruction in muscle atrophy.

In Special Collection:
Mechanobiology 2019

Mechanical forces are generated during epithelial morphogenesis, but how cells maintain adhesion when exposed to these forces is poorly understood. Razzell et al. show that the LIM domain protein Ajuba localizes to adherens junctions under tension in the Drosophila embryo and is required to maintain cell adhesion during epithelial remodeling.

In Special Collection:
Cellular Neurobiology 2018

Nithianandam and Chien show via in vivo imaging that a dynamic population of F-actin termed actin blobs propagates bidirectionally in dendrites and stalls at future branching sites. The F-actin–severing protein Tsr/cofilin is a regulator of actin blob dynamics and dendrite branching.

Astrocytes promote synapse formation during development via secreted factors including thrombospondin family proteins, which act through the neuronal calcium channel subunit α2δ-1. Risher et al. demonstrate that this process requires signaling via the Rho GTPase Rac1 to facilitate the maturation of dendritic spine synapses in the cortex.

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