ON THE COVER
A confocal maximum intensity projection image of an extruding entotic cell cluster in the zebrafish embryonic epidermis. Peridermal cells (green) form a rosette around the extruding cluster. An engulfed basal cell is visible as the accumulation of F-actin (red) inside the extruding peridermal cell at the center of the image. Nuclei are labeled in blue. Image © Armistead et al., 2019. https://doi.org/10.1083/jcb.201905190.
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People & Ideas
Ma and Starr highlight new work from Rahman et al. that reveals new insight into the mechanisms controlling embryonic pronuclei fusion.
Singhal et al. highlight new findings from Schulz et al. regarding the survival-promoting effects of GDPGP1 in neural cells.
Christophe Leterrier previews work from Lee et al. that describes a mechanism by which NKCC1 levels are regulated in GABAergic neurons.
NuMA1 facilitates the assembly of the axon initial segment by promoting the retention of neurofascin-186
Abouelezz and Hotulainen preview work from Torii et al. that describes a role for NuMA1 in the early stages of axon initial segment assembly.
T cell activation requires force production at the immunological synapse. Blumenthal and Burkhardt describe how distinct actin structures contribute to this process, addressing canonical immunological models from a mechanobiology perspective.
From a genome-wide CRISPR screen, Mis et al. identify IPO11 as a required factor for βcatenin-mediated nuclear import and transcription, uncovering a novel mechanism of βcatenin nuclear transport in colorectal cancer.
Rahman et al. analyze the first mitotic division in C. elegans embryos via focused ion beam scanning electron microscopy. They identify novel membrane structures, including three-way sheet junctions, underlying the fusion of the two pronuclei containing the parental genomes.
Maniscalco et al. show that primordial germ cells remodel by assembling a nonmitotic contractile ring. Ring formation requires the RhoGEF ECT-2 and its activator NOP-1 but not centralspindlin, which activates ECT-2 to position the cytokinetic contractile ring during mitosis.
Ems-McClung et al. visualize a RanGTP effector gradient of association between XCTK2 and importin α/β in the spindle. The importins preferentially inhibit XCTK2-mediated antiparallel microtubule cross-linking and sliding, which allows XCTK2 to cross-link parallel microtubules and help focus spindle poles.
Podosomal remodeling of the extracellular matrix by endothelial cells is a key step facilitating sprouting angiogenesis. Collins et al. present Septin2 as a previously unknown facet of the complex regulatory mechanism governing podosome function and endothelial cell invasion.
Girão et al. use structure-guided functional mutants of CLASP2 to show that recognition of growing microtubule plus-ends through EB–protein interaction and the ability to associate with curved microtubule protofilaments through TOG2 and TOG3 domains promote growth and stabilization of kinetochore–microtubules required for poleward flux.
Aurora B localizes to centromeres, but it is unclear if this influences chromosome segregation in mitosis. Liang et al. find that two phospho-histone marks separately recruit Aurora B to centromeres and act redundantly for faithful chromosome segregation. Loss of H3pT3- and H2ApT120-dependent pools of Aurora B at centromeres diminishes error correction efficiency and increases lagging chromosomes in anaphase.
Gradients of Aurora A and B kinase activity at the mitotic spindle are crucial for chromosome alignment. Poser et al. show how Aurora A at the spindle poles promotes chromosome congression by activating the chromokinesin KIF4A.
Clathrin stabilizes microtubules and promotes chromosome alignment during mitosis. Rondelet et al. show that the clathrin–adaptor interaction mechanism is repurposed to recruit GTSE1 to the spindle, which inhibits the microtubule depolymerase MCAK and promotes chromosome alignment by stabilizing nonkinetochore microtubules.
McLamarrah et al. characterize an early step in centriole duplication. They show that Plk4 hyperphosphorylates Ana2, which increases the affinity of Ana2 for the G-box domain of Sas4, promoting Ana2’s accumulation at the procentriole and, consequently, daughter centriole formation.
Reticulon protects the integrity of the ER membrane during ER escape of large macromolecular protein complexes
Escape of large macromolecular complexes induces mechanical stress, which may threaten ER membrane integrity. How the ER responds to this threat remains unknown. Chen et al. demonstrate that the ER morphogenic protein reticulon (RTN) protects ER membrane integrity during ER escape of these complexes.
Grey et al. discover a mechanism by which the epithelial-specific ER stress sensor IRE1β acts as a negative regulator of IRE1α. IRE1β interacts directly with IRE1α to suppress XBP-1 splicing and modify the unfolded protein response to endoplasmic reticulum stress in intestinal epithelial cells.
Zika virus induces the formation of vesicles from ER membrane that form viral replication factories in the ER lumen. Ci et al. show that the Zika NS1 protein plays a key role in this remodeling of the ER as the insertion of the hydrophobic regions of NS1 into the inner leaflet of the ER membrane creates the compartments essential for viral replication.
Rossi et al. describe a novel assay for exocyst in-vesicle tethering. In this assay, gain-of-function mutants in the Exo70 subunit of the exocyst, which bypass Rho/Cdc42 activation in vivo, stimulate vesicle tethering. Single-particle EM studies reveal a structural change responsible for the gain of function.
GDPGP1 and its C. elegans homologue mcp-1 are identified as novel stress-responsive genes in neuronal cells. Stress-induced down-regulation of GDPGP1/mcp-1 reduces cellular glycogen levels and contributes to hypoxia sensitivity and neurodegeneration across species.
Lee et al. show that the local abundance of the chloride importer NKCC1 and timely emergence of GABAergic inhibition are modulated by proteasome distribution, mediated through interactions of proteasomes with the proteasome adaptor Ecm29 and the axon initial segment scaffold protein ankyrin G.
Axon initial segments (AISs) initiate action potentials and regulate the trafficking of vesicles between somatodendritic and axonal compartments. Torii et al. show that NuMA1 is transiently located at the AIS and promotes rapid AIS assembly by inhibiting the endocytosis of neurofascin-186.
This study reveals a novel role of hemidesmosomes in resisting actomyosin-generated cellular tension, which is dependent on mechanical coupling of focal adhesions to hemidesmosomes and inhibition of mechanosensitive signaling. Furthermore, through their ability to influence cellular tension, hemidesmosomes also control the localization of αvβ5 in flat clathrin lattices.
Armistead et al. show that in a bilayered epithelium in vivo, apical cell extrusion of basal cells is achieved via their engulfment by surface cells. In zebrafish hai1a mutants, this constitutes a tumor-suppressive mechanism, revealing a double face of Matriptase.