ON THE COVER
Collage of early C. elegans embryos at different stages of the cell cycle stained for TPXL-1 (red), α-tubulin (green), and DNA (blue). During cytokinesis TPXL-1 activates Aurora A kinase on astral microtubules to clear contractile ring components from the cell poles.
Image © Mangal et al., 2018.
See page 837.
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People & Ideas
Janody previews studies from the Knust and Djiane laboratories that identify Big bang as a new growth regulator in Drosophila melanogaster.
Ewers outlines a toolbox of recombinant secondary nanobodies produced in E. coli, provided open source by the study from Pleiner, Bates, and Görlich.
Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins
Cadwell and Debnath provide a perspective on our emerging understanding of the nonautophagic functions of autophagy-related proteins and their role in disease.
TPXL-1 activates Aurora A to clear contractile ring components from the polar cortex during cytokinesis
During cytokinesis, centrosomal asters inhibit cortical contractility at the cell poles. Mangal et al. provide molecular insight into this phenomenon, showing that TPXL-1, which localizes to astral microtubules, activates Aurora A kinase to clear contractile ring proteins from the polar cortex.
An interaction between myosin-10 and the cell cycle regulator Wee1 links spindle dynamics to mitotic progression in epithelia
Proper spindle orientation must be achieved before anaphase onset, but whether and how cells link spindle position to anaphase onset is unknown. Sandquist, Larson, et al. identify a novel interaction between the motor protein myosin-10 and the cell cycle regulator wee1 that is proposed to help coordinate preanaphase spindle dynamics and positioning with mitotic exit.
The mitotic spindle checkpoint protects cells against chromosome missegregation. Petsalaki et al. show that Chmp4c, a protein in the ESCRT complex, has a surprising role in regulating spindle checkpoint signaling by promoting localization of the RZZ complex to unattached kinetochores.
The conserved paralogous Brr6 and Brl1 promote NPC biogenesis in an unclear manner. Here, Zhang et al. show that both transmembrane proteins transiently associate with NPC assembly intermediates and directly promote NPC biogenesis.
Enucleated cells reveal differential roles of the nucleus in cell migration, polarity, and mechanotransduction
The nucleus plays critical physical roles during cell polarization, migration, and mechanotransduction. Graham et al. explore these processes in its absence. Although polarization and migration occur, cells lacking a nucleus revealed an altered mechanoresponse that is consistent with the nucleus regulating cell contractility.
Cortical microtubule arrays of plants feature treadmilling polymers that are dynamic at both ends, but how the minus ends are controlled is unclear. Nakamura et al. show that SPR2 dynamically tracks and stabilizes microtubule minus ends in Arabidopsis thaliana, which regulates their severing potential and reorients cortical arrays in response to light perception.
Formins promote actin nucleation but also influence the microtubule cytoskeleton. Fernández-Barrera et al. show that formins activate the MRTF-SRF transcriptional complex to induce expression of the α-TAT1 gene encoding the enzyme responsible for tubulin acetylation, thus revealing a mechanism underpinning the relationship between formins and tubulin acetylation.
Interactions between actin nucleators and the exocyst in yeast and mammals control membrane remodeling. van Gisbergen et al. now describe For1F, a fusion of an exocyst subunit (Sec10) and an actin nucleation factor (formin), retained in the moss lineage for more than 170 million years, which provides unique insight into the regulation of exocytosis by actin.
The ER–mitochondrial encounter structure (ERMES) physically links ER and mitochondrial membranes in yeast, but it is unclear whether ERMES directly facilitates lipid exchange between these organelles. Kawano et al. reveal by reconstitution experiments that a complex of Mmm1–Mdm12, two core subunits of ERMES, functions as a minimal unit for lipid transfer between membranes.
Rab18 promotes lipid droplet (LD) growth by tethering the ER to LDs through SNARE and NRZ interactions
Lipid incorporation from the ER to lipid droplets (LDs) influences LD growth and intracellular lipid homeostasis. Xu et al. identify Rab18 as an important regulator of LD dynamics: activated Rab18 binds to ER-associated proteins such as the NRZ complex and SNAREs. The Rab18-NRZ-SNARE complex tethers LDs to the ER, facilitating lipid incorporation and LD growth.
Mammalian autophagosomes mature into autolysosomes through SNARE-driven processes that include syntaxin 17 (Stx17). Kumar et al. show that Stx17 interacts with mammalian Atg8s and with the small guanosine triphosphatase IRGM and that both IRGM and mAtg8s help recruit Stx17 to autophagosomes.
The Cullin-3–Rbx1–KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB
The RhoA GTPase controls endothelial cell migration, adhesion, and barrier formation but the role of RhoB is unclear. Kovačević et al. now discover that RhoB is ubiquitinated by the CUL3–Rbx1–KCTD10 complex and that this is a prerequisite for lysosomal degradation of RhoB and the maintenance of endothelial barrier integrity.
How signaling and scaffolding proteins are coordinated apically to control junctional tension and hence epithelial cell growth is unclear. Tsoumpekos et al. identify the Drosophila scaffolding protein Big bang as a novel regulator of growth in epithelial cells of the wing disc by showing that big bang ensures proper junctional tension and apical cytocortex organization.
The apical scaffold big bang binds to spectrins and regulates the growth of Drosophila melanogaster wing discs
During development, cell proliferation is regulated, ensuring that tissues reach their correct size and shape. Forest et al. show that the Drosophila melanogaster scaffold protein big bang (Bbg) controls epithelial tissue growth without affecting epithelial polarity and architecture. Bbg interacts with spectrins at the apical cortex and promotes Yki signaling and actomyosin contractility.
β-Catenin is a transcription cofactor proposed to be released from E-cadherin upon mechanically induced phosphorylation. However, evidence for this mechanism is lacking. Gayrard et al. show instead that during epithelial-to-mesenchymal transition, Src- and multicellular confinement–dependent FAK-induced cytoskeleton remodeling causes E-cadherin tension relaxation and phosphorylation-independent β-catenin nuclear translocation from the membrane.
Cell–cell adhesion and cell shape are regulated at adherens junctions during embryonic morphogenesis. Beati et al. show that the Drosophila LIM domain protein Smallish interacts with Bazooka, Canoe, and Src42A at adherens junctions. Loss-of-function and gain-of-function phenotypes reveal a function for Smallish in regulation of actomyosin contractility and cell shape.
Mechanisms that sense and regulate epithelial morphogenesis and homeostasis are incompletely understood. Schepis et al. provide evidence that protease-activated receptor Par2b and matriptase, a membrane-tethered protease, can regulate apical extrusion and other epithelial responses involved in tissue remodeling and inflammation.
Urbina et al. use a new computer-vision image analysis tool and extended clustering statistics to demonstrate that the spatiotemporal distribution of constitutive VAMP2-mediated exocytosis is dynamic in developing neurons. The exocytosis pattern is modified by both developmental time and the guidance cue netrin-1, regulated differentially in the soma and neurites, and distinct from exocytosis in nonneuronal cells.
All mammalian cells release small endosome-derived exosomes that function in intercellular communication, but the secretion process is poorly understood. Verweij et al. developed a live-imaging approach and demonstrate that external cues can trigger exosome release from a subpopulation of multivesicular bodies by phosphorylating the target membrane SNARE SNAP23 at serine residue 110.
Pleiner, Bates, and Görlich introduce anti–mouse and anti–rabbit IgG nanobodies that can be produced in E. coli and fused to reporters or labeled fluorescently to create bright and specific detection reagents with unique advantages over conventional polyclonal secondary antibodies.
Correction: Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling