Issues

Summary: In this Review, we outline the machinery involved in mitochondrial fission including the recent discovery of Dnm2 as the final executor of membrane scission. An updated model of fission is presented.

Summary: We review results showing that conjugation of the ubiquitin-like protein ISG15 (ISGylation) tags newly synthesized proteins as suspicious and inhibits exosome secretion to prevent the spreading of pathogens and protein aggregates.

Highlighted Article: Through an optogenetic approach, differences in the contributions of Rac and Cdc42 to directed migration are analyzed. Cdc42 can stabilize protrusions and directed migration via fibronectin secretion while Rac cannot.

Summary: Our study uncovers a novel function of Dronc in mediating the γH2Av response via ATM kinase, which, independent of its cell death function, facilitates DNA damage signalling and perhaps repair.

Highlighted Article: A novel protein complex connects vesicle fusion with Cdc42p activation. Genetic and protein interaction data suggest that its central members Boi1p and Boi2p chaperone the formation of the docking complex.

Summary: The cytoskeleton transports premature termination codon-containing mRNAs to be degraded by nonsense-mediated decay or to be read through in specific cytoplasmic foci called readthrough bodies.

Highlighted Article: Cdk5-mediated degradation of Mcl-1 by direct phosphorylation promotes neurotoxicity. Mcl-1 upregulation, or Cdk5 inhibition, is potentially an attractive therapeutic strategy for preventing neurodegeneration in AD.

Summary: The stress-response proteins IRE1 and XBP1 are developmentally essential in metazoans. We identify the source of the physiological stress in Drosophila and determine the molecular requirements for stress response signaling.

Highlighted Article: Enzymes regulating membrane cholesterol concentrations affect the formation and dissociation of signalling complexes in response to amyloid-β, and are involved in synapse degeneration induced by amyloid-β.

Summary: Multiple cis-acting signals direct the first step in localization of oskar mRNA. These signals are collectively strong but individually weak, a property essential for later steps of localization.

Highlighted Article: Net1 associates with Smad2 in the nucleus in a GEF-independent manner and facilitates Smad2 transcriptional activity to guide mesendoderm development in zebrafish.

Summary: NFATc1 and NFATc4 are required for the correct transformation of human muscle progenitors into myotubes, which is an essential process for muscle regeneration.

Summary: We present the first Sharpin interactome and identify a new function for Sharpin in cytoskeleton function. Sharpin binds the Arp2/3 complex, which promotes lamellipodium formation.

Summary: TRIM65 serves as a prognostic factor for poor outcome in HCC, and exerts oncogenic activities via ubiquitylation of Axin1 to activate the β-catenin signaling pathway.

Summary: IL6-seeking cells were engineered to target synthetic IL6 sources using a chimeric receptor and a previously engineered Ca²⁺-activated RhoA. Such cells could potentially be used to target senescence.

Summary: L-leucyl-L-leucine methyl ester (LLOMe) permeabilizes lysosomal membranes and destabilizes lysosomal enzymes. LLOMe-induced apoptosis is independent of cysteine cathepsin proteolytic activities in the cytosol.

Summary: CG2254/Ldsdh1 targets a subset of lipid droplets (LDs) within cells. We identify a distinct sequence stretch that is sufficient for this LD subset localization, and characterize LD diversification in greater detail.

Summary: Dictyostelium GflB, known as a Rap1 GEF, interacts with F-actin via its N-terminal villin headpiece (VHP)-like domain and regulates macropinocytic and phagocytic cup formation and retraction.

Summary: A cell shape-based visual screen of S. pombe in the presence of actinomycete-derived bioactivities and an explanation for the phenotypes following identification of the compounds.