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Issues

In Focus

Study describes how epithelial cells process keratin 6a to generate antimicrobial peptides that prevent bacteria from colonizing the cornea.

People & Ideas

Song studies the trafficking and biological activities of cholesterol.

In Memoriam

Spotlight

Giacomello and Scorrano discuss work from Mattie et al. redefining mitofusin topology and questioning the current models of mitochondrial fusion.

O'Neill and O'Neill discuss Platt et al.’s findings that LINE1 elements are key to control of replication timing by ASAR long noncoding RNAs.

Hyungsoo Kim and Ze’ev Ronai preview work from Colaluca et al. that reveals the function of Numb exon 3–containing isoforms in the formation of a fuzzy complex with Mdm2 and the regulation of p53 stability.

Review

Lawson and Ridley review the roles of GEFs and GAPs in forming complexes that regulate Rho GTPases for cell migration and invasion.

Hansen et al. review the potential dual helpful and harmful roles of microglia in the development and progression of Alzheimer’s disease.

Report

Neuronal stimulation leads to the expression of immediate early genes (IEGs). Azad et al. show that neuronal depolarization induces replacement of the linker histone H1 by PARP1 at IEG promoters in a manner that requires H1 phosphorylation and H1 poly-ADP ribosylation.

The p97 adapter p37 was known to regulate spindle orientation in human cells, but the mechanism was unknown. In this study, we show that it limits the cortical recruitment of NuMA in a PP1–Repo-Man–dependent manner. This study identifies a novel pathway controlling cortical NuMA localization.

In Special Collection:
Lipid and membrane biology 2019

In yeast, the ER stress surveillance (ERSU) pathway ensures that daughter cells inherit a functional ER during ER stress. Piña et al. show that phytosphingosine (PHS) levels increase during ER stress and PHS alone is sufficient to activate the hallmarks of ERSU activation: cER inheritance block, septin mislocalization, and Slt2 phosphorylation.

The mitofusin GTPases that mediate mitochondrial fusion in metazoans are thought to span the mitochondrial outer membrane twice. Phylogenetic, bioinformatic, and biochemical analyses now reveal a single membrane-spanning region with a domain in the intermembrane space that is redox regulated, prompting a reevaluation of the molecular mechanisms that drive fusion.

TBC1D7 negatively regulated cell growth as a subunit of the tuberous sclerosis complex (TSC). Ren et al. show that dTBC1D7 regulates systemic growth by modulating the biosynthesis and release of insulin-like peptide 2 independently of TSC in Drosophila.

Article

The endoribonuclease DICER facilitates chromatin decondensation during lesion recognition following UV exposure. Chitale and Richly show that DICER mediates the recruitment of the methyltransferase MMSET, which catalyzes the dimethylation of histone H4 at lysine 20 and facilitates the recruitment of the nucleotide excision repair factor XPA.

Proper chromosome duplication is critical for genome integrity and normal cellular function. Platt et al. show that the lncRNA genes ASAR6 and ASAR15 control chromosome-wide replication timing via the antisense strand of L1 retrotransposons located within ASAR6 and ASAR15 RNAs.

Sato-Carlton et al. show that the partitioning of Caenorhabditis elegans chromosomes into two domains that differentially mediate separation in meiosis I and II requires phosphorylation of the synaptonemal complex protein SYP-1, which in turn promotes Polo-like kinase 2 localization to the synaptonemal complex.

In Special Collection:
Stem Cells and Development 2018

Large-scale knockout studies suggest that most miRNAs are phenotypically dispensable. However, Kavaler et al. show here that developmental specification toward a non-neuronal fate in the Drosophila melanogaster peripheral sensory organ lineage depends critically on mir-279/996 repression of the Notch repressor Insensible.

N-Glycosylation and GPI anchoring of proteins occur in the endoplasmic reticulum (ER). Liu et al. revealed N-glycans participate in quality control and temporal ER retention of GPI-anchored proteins (GPI-APs), ensuring their correct folding and GPI processing before exiting from the ER. Chronic ER stress induced exposure of unprocessed GPI-APs on the cell surface.

In yeast, the TRAPP complexes activate Rab1 with TRAPPII also activating Rab11, but less is known about the two TRAPPs in metazoans. Riedel et al. show that in Drosophila melanogaster, TRAPPIII is an essential Rab1 activator, and TRAPPII activates Rab1 and Rab11 and becomes essential when an unrelated Rab11 activator is deleted.

The mechanisms underlying microtubule-dependent long-distance movement of peroxisomes in mammalian cells are unclear. Okumoto et al. identify splicing variants of human mitochondrial Rho GTPase-1 (Miro1) that localize to peroxisomes and that link these organelles to microtubule-dependent transport complexes including TRAK2.

Gong et al. show in multiple cell types that a mitochondrial-associate peptide, humanin, activates chaperone-mediated autophagy (CMA) by stabilizing the interaction between HSP90 and CMA substrates, thereby protecting cells from stressor-induced cell death.

In Special Collection:
Lysosomes and Endocytosis 2018

Adipocytes secrete fatty acid binding protein 4, which influences glucose production in hepatocytes and insulin secretion in pancreatic β-cells, but the mechanisms of its secretion are unclear. Villeneuve et al. show that FABP4 is secreted unconventionally through enclosure within endosomes and secretory lysosomes.

The protein Flower mediates the calcium-dependence of synaptic vesicle endocytosis in Drosophila. Chang et al. show that Flower is predominantly localized on intracellular vesicles that move to the synapse upon target cell contact and that Flower is required for efficient endocytosis of cytotoxic granules in T cells.

This work describes a crucial role for the transcription factor Srf and F-actin scaffold to drive muscle stem cell fusion in vitro and in vivo and provides evidence of how actin cytoskeleton architecture affects myoblast fusion in vertebrates.

In migrating cells, actin underlies formation of pseudopods, filopods, and blebs. Davidson et al. use multiple knockouts in Dictyostelium to show that WASP family proteins SCAR/WAVE and WASP compete with the formin dDia2 for actin, influencing pseudopod and bleb formation.

Wigerius et al. identify the polarity protein AMOT-130 as vital for dendritic spine morphogenesis. They show that reduced Lats1 kinase activity in the neonatal brain is required for the recruitment of AMOT-130 to postsynaptic compartments to stabilize dendritic spines.

In Special Collection:
Special Focus

Chan et al. show that epithelial cells respond to bacterial components in the environment by releasing subunits of the keratin 6a (K6a) filament network to the cytosol for degradation by the ubiquitin–proteasome system. This generates antimicrobial peptides from K6a that are important for innate defense of the mucosal surface.

In Special Collection:
Cell Biology of Cancer 2018

Numb regulates the activity of the tumor suppressor p53 by inhibiting Mdm2. This study from Colaluca et al. highlights the structural and molecular bases of Numb–Mdm2 interaction and shows how Numb splicing impacts specifically on p53 regulation and breast cancer prognosis.

Epithelial-to-mesenchymal transition is implicated in metastasis. Viotti et al. show that the histone methyltransferase SUV420H2 favors the mesenchymal identity in pancreatic tumor cells by silencing key drivers of the epithelial state. High levels of SUV420H2 also correlate with a loss of epithelial characteristics in invasive cancer.

Tools

SxIP-iLID is a novel optogenetic tool designed to assess the temporal role of proteins on microtubule dynamics. The authors establish that optogenetic cross-linking of microtubule and actin networks decreases MT growth velocities and increases the cell area void of microtubules.

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