ON THE COVER
Artistic representation of a developing zebrafi sh embryo (solid cyan lines). Within the outlines of the hindbrain and the retinas, a collage of microscopy images of neuroepithelial cells represents the characteristic positioning of the nucleus (white) and the cytoskeleton (diff use cyan) before mitosis. Image © Yanakieva et al., 2019 See page 3272.
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People & Ideas
Gay and Ito preview work from the Greco laboratory showing that the hair follicle epithelium suppresses tumorigenesis through regeneration.
Elena Pasquale previews work from Gong et al. that elucidates the role of Gulp1 in the regulation of EphB/ephrinB-mediated trogocytosis.
Hayward et al. identify BUBR1-associated PP2A-B56 as the main MPS1 T-loop phosphatase in mammalian cells. They show that expression of a constitutively active form of MPS1 refractory to PP2A-B56 results in exaggerated MPS1-mediated error correction and impaired cell cycle progression.
Chen et al. reconstitute endocytosis in a cell-free system and show that cargo sorting requires the dynamic dissociation of clathrin during the growth phase of the clathrin-coated pit formation.
Healthy tissues can harbor cancer-associated mutations without developing tumors, yet the mechanisms behind this apparent tolerance are unclear. In this work, we demonstrate that the hair follicle skin epithelium uses regeneration as a means of suppressing Ras-driven oncogenic growth.
Phosphorylation of kinetochore proteins destabilizes improper kinetochore–microtubule attachments. Asai et al. find that SET/TAF1, an inhibitor of the PP2A phosphatase, binds shugoshin 2 and corrects erroneous kinetochore–microtubule attachment by maintaining Aurora B kinase activity. Therefore, SET has a key role in establishing chromosome bi-orientation by balancing Aurora B and PP2A activity.
In mitosis, the outer kinetochore is assembled to signal the spindle assembly checkpoint and to attach chromosomes to spindle microtubules. Bonner et al. demonstrate that outer kinetochore assembly requires the enrichment of Aurora B kinase at the inner kinetochore by the conserved central region of INCENP.
Coronin 1A depletion restores the nuclear stability and viability of Aip1/Wdr1-deficient neutrophils
Bowes et al. show that in zebrafish embryos deficient in the cofilin cofactor AIP1/Wdr1, neutrophils display F-actin as cytoplasmic aggregates, spatially uncoupled from active myosin, then undergo a progressive unwinding of their nucleus followed by eruptive cell death. This adverse phenotype is fully rescued by depletion of another cofilin cofactor, coronin 1A.
Using quantitative live imaging in the developing zebrafish embryo, Yanakieva et al. show that distinct actin-dependent mechanisms position nuclei in neuroepithelia of different morphology. In curved neuroepithelia, a novel formin-dependent mechanism is discovered for which the authors propose a proof-of-principle theoretical model.
FIGNL1 associates with KIF1Bβ and BICD1 to restrict dynein transport velocity during axon navigation
Atkins et al. identify a new role for Fidgetin-like 1 in motor axon navigation via its regulation of bidirectional axonal transport. They show that Fidgetin-like 1 binds Kif1bβ and the opposed polarity-directed motor dynein/dynactin in a molecular complex and controls circuit wiring by reducing dynein velocity in developing motor axons.
A molecular recognition feature mediates ribosome-induced SRP-receptor assembly during protein targeting
Hwang Fu et al. show that a molecular recognition feature (MoRF) in the mammalian signal recognition particle (SRP) receptor accelerates SRP-receptor assembly in response to the ribosome. The MoRF functionally replaces the bacterial SRP RNA to sense cargo loading and activate cotranslational protein targeting.
Lipolysis and lipophagy are thought to be distinct mechanisms for lipid droplet catabolism. In hepatocytes, Schott et al. report that these pathways may operate synergistically: the lipolysis enzyme ATGL targets large LDs upstream of lipophagy, which is restricted to small LDs.
Takahashi et al. perform a genome-wide CRISPR screen using the HaloTag-LC3 assay to gain insight into the mechanisms of phagophore closure. They identify a role for VPS37A in coordinating the ESCRT assembly on the phagophore for membrane closure.
Invasive cancer cells degrade and invade into the extracellular matrix by expressing the matrix metalloproteinase MT1-MMP at invadopodia. Miyagawa et al. show that MT1-MMP uses the ER-Golgi SNARE Bet1 to facilitate its own transport to the plasma membrane through their interaction in a cholesterol-rich milieu.
Tight junctions (TJs) are a key component of barriers formed by polarized epithelial cells. Otani et al. found that the scaffolding proteins ZO-1/ZO-2 are essential for TJ formation and epithelial polarity. Claudins regulate the TJ strand and electrolyte permeability barrier, while JAM-A regulates membrane apposition and the macromolecule permeability barrier. Claudins and JAM-A act redundantly in regulating epithelial polarity.
Silver et al. show that the RhoGEF Cysts links apical polarity proteins to Rho1 and myosin activation at adherens junctions to support junctional and epithelial integrity in the Drosophila ectoderm.
Actin assembly by APC maintains proper organization and dynamics of F-actin at focal adhesions. This, in turn, impacts the organization of other molecular components and the responsiveness of focal adhesions to microtubule capture and autophagosome-induced disassembly.
Kindlin-3 regulates podosome stability by recruiting leupaxin to podosomes, which in turn controls PTP-PEST activity and paxillin phosphorylation. Kindlin-3 deficiency allows formation of initial adhesion patches containing talin, vinculin, and paxillin, whereas paxillin family proteins are dispensable for podosome formation.
Trogocytosis, intercellular cannibalism distinct from phagocytosis, occurs when cells rearrange during development. Here, Gong et al. reveal that trogocytosis induced by ephrins and Eph receptors involves phagocytic adaptor protein Gulp1, Rac-specific guanine nucleotide exchange factor Tiam2, and endocytic GTPase dynamin. These results suggest that ephrin/Eph-induced trogocytosis uses phagocytosis-like mechanisms.
Using a microfluidic method, it was found that YAP and TAZ are novel regulators of single-cell size and act independently of mTOR. YAP also influences cell cytoplasmic pressure and acts together with cytoskeletal tension to influence cell cycle progression.
Lo and colleagues show that CEP83 is a TTBK2 substrate and further demonstrate that TTBK2-dependent CEP83 phosphorylation is important for the early stages of ciliogenesis, including ciliary vesicle docking and CP110 removal.
Pericytes play important roles in the repair of the blood–brain barrier (BBB). Nakamura et al. show that an ECM protein, perlecan, maintains BBB integrity and regulates pericyte recruitment after ischemic stroke through the cooperative function of PDGFRβ and integrin α5β1.