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  • Cover Image

    Cover Image

    issue cover

    ON THE COVER
    Confocal image of a late cytokinetic HeLa cell showing microtubules at the cytokinetic bridge (red), nuclei (blue), and Hook2 at the midbody ring (green). Image © Dwivedi et al., 2019.
    See page 871.

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ISSN 0021-9525
EISSN 1540-8140

People & Ideas

Sharma investigates vesicular trafficking to lysosomes and how pathogens hijack the endolysosomal system during infection.

Spotlights

Alper and Zanic highlight new findings from Sallé et al. about the forces that can control asymmetric cell division.

Sassano and Agostinis preview two papers from the De Matteis laboratory that monitor and identify new determinants of ER–TGN contact sites.

Katharina Schlacher previews work from Chow et al. that links ATM activation in cerebellar Purkinje cells with mitochondrial function and ATP production during periods of high energy demand.

Yudushkin highlights a new reporter from the Hammond laboratory revealing that PI(3,4)P2 primarily derives from PI(3,4,5)P3 dephosphorylation at the plasma membrane.

Viewpoint

Raote and Malhotra suggest a revision of the long held view of vesicles as the only carriers of secretory cargo.

Discussion/Inside Look

Hui details the cell biology underlying the action of immune checkpoint inhibitors.

Reviews

Bonello and Peifer summarize recent advances in our understanding of how the scaffolding protein Scribble regulates polarity, adhesion, proliferation, and neuronal function.

Zhao and Zhang summarize recent advances in our molecular understanding of the maturation of nascent autophagosomes into degradative autolysosomes in multicellular organisms.

Reports

Sallé et al. use magnetic beads to cluster dynein minus end activity and generate controlled asymmetric cortical pulling domains in sea urchin zygotes. Experimental and modeling studies show that asymmetric divisions may be triggered by a reduction in centering forces under constant cortical pulling forces.

Venditti et al. identify FAPP1 as a new determinant of ER–trans-Golgi network contacts that interacts with the phosphoinositide phosphatase Sac1 and promotes its phosphatase activity. The results suggest that, by controlling PI4P levels, FAPP1 acts as a gatekeeper of cargo Golgi exit.

The regulation of organelle abundance is crucial for cellular health and function. In this study, Riccio et al. show that the mitochondrial deubiquitinase USP30 localizes to peroxisomes, where it regulates PEX2-dependent pexophagy potential and demonstrates its potential as a therapeutic target for the treatment of Zellweger’s spectrum disorders.

The retrograde microtubule motor cytoplasmic dynein is fundamental for mammalian brain development. Gonçalves et al. identify distinct roles for dynein cargo-binding subunits, the light intermediate chains, in neocortical development and uncover a novel function for dynein in terminal somal translocation of neurons.

Articles

Delaney et al. show that the unstructured domain cofactor LIN-65 is essential for the stable formation of heterochromatic foci. It stably interacts with the H3K9 methyltransferase MET-2/SETDB1 and modulates MET-2 nuclear localization, activity, and H3K9me-mediated silencing in C. elegans.

How resident inner nuclear membrane (INM) proteins are turned over is unclear. Koch et al. identify an APC/C-dependent mechanism controlling the degradation of Mps3, a conserved integral protein of the INM.

Menin and glucagon-like peptide 1 (GLP-1) pathways play central yet opposing roles in regulating β cell function, with menin suppressing and GLP-1 promoting β cell function. Xing et al show that GLP-1 induces PKA-mediated phosphorylation of menin. Phosphorylation of menin triggers its interaction with nuclear actin to relieve menin’s transcriptional repression and increase insulin production.

Hook proteins are conserved dynein adaptors that promote the assembly of dynein–dynactin motor complexes. Dwivedi et al. show that Hook2 is a novel mitotic adaptor that mediates dynein–dynactin–dependent anchoring of the centrosome to the nuclear envelope and microtubule nucleation from mitotic centrosomes. In addition, Hook2 is needed for the dynactin-dependent targeting of the centralspindlin complex to the midzone for normal cytokinesis.

Schiffhauer et al. use mathematical modeling of Dictyostelium myosin II and experimental approaches in mammalian cells to demonstrate that multiple inputs modulate the ability of myosin II to assemble into filaments. These inputs integrate to govern the myosin II mechanoresponsiveness.

Oxidative stress, resulting from neuronal activity and depleted ATP levels, activates ATM, which phosphorylates NRF1, causing nuclear translocation and up regulation of mitochondrial gene expression. In ATM deficiency, ATP levels recover more slowly, particularly in active neurons with high energy demands.

Trafficking of procollagen is essential for normal cell function. Here, imaging of GFP-tagged type I procollagen reveals that it is transported from the endoplasmic reticulum to the Golgi, without the use of large carriers.

Mutations in mysterin cause cerebrovascular moyamoya, but the mechanism of pathogenesis is unknown. Sugihara et al. report that mysterin stabilizes cytoplasmic lipid droplets through the activity of ATPase and ubiquitin ligase. Disease-associated mutations in mysterin impair this process, suggesting a potential link between moyamoya disease and metabolism.

This study reveals a previously unappreciated interplay between Rab5 GTPases and TORC2 function in yeast. TORC2 signaling stimulates the Rab5-specific guanine nucleotide exchange factor Muk1, and, in turn, activated Rab5 GTPases, especially Vps21, act as positive effectors to stimulate TORC2 activity.

Lee et al. show that methionine triggers Ppz phosphatase-dependent dephosphorylation of the E3 ubiquitin ligase adaptor Art1. Art1 dephosphorylation promotes its interaction with the methionine transporter Mup1, as well as subsequent endocytosis and degradation of Mup1 in the vacuole.

Patrón et al. show that presynaptic Drosophila DCAF12 is required for neurotransmitter release and homeostatic synaptic plasticity at neuromuscular junctions. Postsynaptic nuclear DCAF12 controls the expression of glutamate receptor IIA subunits in cooperation with Cullin4 ubiquitin ligase.

By performing an in vivo screen in Drosophila melanogaster, Scholz, Ehmann, et al. identify Complexin as a functional interaction partner of Bruchpilot. The two proteins mediate a physical attachment of synaptic vesicles to the active zone cytomatrix and promote rapid, sustained synaptic transmission.

Mutations in the essential retinal protein retinoschisin (RS1) cause a form of macular degeneration. Heymann et al. use cryo-EM to show that RS1 assembles into branched networks that may play a stabilizing role in maintaining the integrity of the retina.

Gunawan et al. analyze at single-cell resolution collective endocardial cell migration into the extracellular matrix and the cellular rearrangements forming leaflets during zebrafish heart valve formation. They show that focal adhesion activity driven by Integrin α5β1 and Talin1 are essential to drive cardiac valve morphogenesis in zebrafish.

Tools

Venditti et al. develop a novel FRET- and FLIM-based approach to monitor ER–trans Golgi network (TGN) contacts and identify VAP proteins, OSBP1, ORP9, and ORP10 as required to maintain contacts. OSBP1 and ORP9 play redundant structural roles, whereas ORP10’s requirement depends on its ability to transfer phosphatidylserine to the TGN.

A sensitive new genetically encoded lipid biosensor for PI(3,4)P2 has been developed, revealing the lipid is mainly produced via PIP3 after activation of class I PI3K signaling. The PI(3,4)P2 is also a direct substrate for the tumor suppressor lipid phosphatase PTEN.

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