Issues

Benzi and Piatti preview work from Cordeiro and colleagues that describes new insights into the regulation of PLK1 during mitotic checkpoint silencing.

Taylor and Pelisch preview work from the McNally group suggesting a new kinetochore-based model of chromosome segregation in C. elegans oocyte meiosis.

Zarnescu previews work by the Lerit laboratory highlighting a role for FMRP in ensuring centrocortin mRNA localization to centrosomes, which is needed for cell division and embryonic development.

Higgs and colleagues review the emerging field of cytoskeletal lysine acetylation and discuss impacts of actin acetylation on its cytoplasmic and nuclear functions.

Seoane et al. discuss how inflammation driven by the multimolecular NLRP3–inflammasome complex is dependent on organelle dysfunction.

Cordeiro et al. show that PLK1 amplifies the spindle assembly checkpoint signal in an autonomous manner by binding to the BUB complex. They also demonstrate that kinetochore phosphatases are needed to antagonize this auto-catalytic loop to shut down the checkpoint.

Mitochondrial-derived compartments (MDCs) regulate the mitochondrial proteome in response to nutrient stress. English et al. now show that the ERMES complex and the conserved GTPase Gem1 promote MDC biogenesis at sites of contact between the endoplasmic reticulum and mitochondria.

A primordial function of the cGAS/STING pathway may be to induce LC3B lipidation. Fischer et al. show cGAMP-activated STING induces the V-ATPase to recruit ATG16L1 for lipidation of LC3B onto single-membrane perinuclear vesicles. The bacterial effector SopF blocks this pathway, suggesting roles in host defense.

Meiotic anaphase has been reported to be mediated by kinetochore-independent pushing forces in C. elegans. Danlasky et al. find that depletion of kinetochore proteins reduces pulling forces and prevents successful separation of homologous chromosomes during C. elegans meiosis.

Kornakov et al. investigate mechanisms of bipolar spindle assembly, a critical prerequisite for accurate chromosome segregation in mitosis. They define the molecular organization of an interaction interface between the conserved microtubule plus-end tracking protein EB1 and the minus-end motor Kinesin-14 and demonstrate with specific mutations that this complex is required for proper organization of the metaphase spindle.

Watanabe et al. show that centrioles and their associated pericentriolar matrix can independently support spindle assembly. They delineate how the pericentriolar matrix acts without centrioles and describe cancer cell lines in which spindles can assemble in the absence of both centrioles and pericentriolar matrix.

Little is known about the functional importance of mRNA localization to centrosomes. Ryder et al. survey RNA localization to centrosomes within Drosophila embryos and show that regulation of centrocortin mRNA by FMRP ensures normal mitosis and embryonic viability.

NuMA disruption causes nuclear defects, and it was unclear if this is due to NuMA's essential spindle function. Serra-Marques et al. show that NuMA keeps chromosomes together at nuclear formation and promotes a mechanically robust nucleus independently of its spindle function.

How cells respond to deleterious effects imposed by disrupted nuclear pore complex (NPC) assembly is not well defined. Lord and Wente demonstrate that nuclear envelope–vacuole interactions expand in response to perturbed NPC assembly to promote viability, nuclear envelope remodeling, and proper NPC biogenesis.

Hebbar et al. examine morphogenesis of the apical photosensitive plasma membrane of Drosophila photoreceptors. Using mutants exhibiting growth defects, they identify hydroxylated sphingolipid biosynthesis as a regulator of rhabdomere growth. Hydroxylated sphingolipids regulate Rab11-mediated trafficking of Rhodopsin, a major structural component of rhabdomeres.

Endicott et al. report that inhibition of class I PI3K activates chaperone-mediated autophagy (CMA) in cultured cells and mice. Selective inhibition of class III PI3K does not activate CMA. This work disentangles previously misunderstood roles of PI3Ks in CMA regulation.

Oxidative stress is a major risk factor for multiple disorders, including cataracts. The current study uncovers a unique mechanism that transports nutrients and antioxidants to maintain lens homeostasis and transparency. This process is fulfilled through a collaboration between integrin molecules and connexin channels.

Grimm, Dierdorf et al. identify the Ser/Thr phosphatase PPM1F as the critical enzyme controlling a phospho-switch in the integrin β subunit. Dephosphorylation of the integrin T788/T789 motif by PPM1F orchestrates the binding of filaminA versus talin/kindlin-2 and determines integrin activity.

Fibronectin–integrin interactions through the Arg-Gly-Asp cell binding motif play crucial roles in cellular functions. Benito-Jardón and colleagues, using force spectroscopy and mouse genetics, show that neither α5β1 nor αv-class integrins bind to RGD-deficient fibronectin and that αv-class integrins retain normal binding to a mutated RGE motif.

Koyama-Honda et al. developed high-speed single-molecule imaging and found that CD59 clusters and GM1 clusters induced in the plasma membrane outer leaflet–generated nanoscale transbilayer rafts, which continually and transiently recruited Lyn and H-Ras in the inner leaflet by cooperative raft–lipid interactions.

Dendrite pathology is a prominent early feature of neurodegenerative diseases. Using dendritic arborization neurons of Drosophila, Han et al. show that Relish/NF-κB contributes to dendrite and behavioral defects in animal models for polyglutamine diseases and amyotrophic lateral sclerosis via transcriptionally upregulating Tup.

Shinde et al. find that activation of G protein–coupled receptors (GPCRs) inside cilia triggers formation of ubiquitin chains onto the receptors via β-arrestin and that ubiquitin chains commit the GPCRs for exit from cilia.

Mateska et al. describe a mechanism restricting the range of SHH pathway activation in adrenal gland to cells with ARL13B-positive primary cilia that are in physical contact with SHH-producing cells. Cancerous adrenocortical cells evade this restriction by ectopically activating SHH targets in response to TGF-β.