Issues
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Cover Image
Cover Image
On the cover
Loss of CRMP-1 in MDCK cells results in a loss of cortical actin, extensive cell spreading in the plane of the substrate, and holes in the epithelial sheet. Actin is shown in green, E-cadherin is in red, and the nucleus is in blue. Image © 2017 Yu-Kemp et al.
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In Focus
Mitochondria deliver a gut check to intestinal stem cells
Mitochondrial turnover regulates stem cell proliferation and tissue homeostasis in Drosophila intestines.
People & Ideas
Ann Miller: Shaping cells and scientists
Miller studies how the cytoskeleton controls cellular shape change.
Spotlight
RNA gets in phase
Saha and Hyman discuss recent work published by Jain and Vale in Nature documenting RNA phase transitions in repeat expansion disorders.
Strength in numbers: Phosphofructokinase polymerization prevails in the liver
Zaganjor et al. preview work from Webb et al. that shows that the liver-specific isoform of the glycolysis enzyme PFK1 can assemble into filaments and localize to distinct puncta near the plasma membrane.
De novo telomere addition at chromosome breaks: Dangerous Liaisons
Churikov and Géli discuss recent work from Ouenzar et al. on the repression of telomerase at DNA double-strand breaks.
Tubulin isotype specificity in neuronal migration: Tuba8 can’t fill in for Tuba1a
Kawauchi previews work from the Francis group studying tubulin isotype-specific changes in microtubule organization and neuronal migration in vivo.
Lysosomes convene to keep the synapse clean
Kononenko highlights Goo et al.’s discovery that lysosomes can be positioned in neuronal dendritic spines in response to synapse activity.
More than a mere supply of monomers: G-Actin pools regulate actin dynamics in dendritic spines
Katalin Schlett previews the study by Lei et al., which reveals that dendritic spines contain local pools of G-actin that are dynamically regulated in response to synaptic activity by profilin and PIP3.
Review
Dynamic ubiquitin signaling in cell cycle regulation
Gilberto and Peter discuss the role of ubiquitylation in the regulation of DNA replication and mitosis.
Report
F-actin prevents interaction between sperm DNA and the oocyte meiotic spindle in C. elegans
After fertilization, interactions between sperm and egg DNA must be prevented before the completion of female meiosis. Panzica et al. show that cortical tethering by F-actin prevents contact between the paternal DNA and the meiotic spindle.
Translational regulation of viral secretory proteins by the 5′ coding regions and a viral RNA-binding protein
The two influenza glycoproteins encode N-terminal targeting sequences that interact with SRP to direct their synthesis at the endoplasmic reticulum. Nordholm et al. show that in addition to coding for endoplasmic reticulum–targeting sequences, these 5′ mRNA regions also function as translational regulatory elements that are controlled by a viral RNA-binding protein.
ER stress causes widespread protein aggregation and prion formation
ER stress results in widespread aggregation of proteins that are not localized to the ER or are part of the secretory system. Hamdan et al. demonstrate that amorphous and amyloidogenic protein aggregation is an indirect consequence of perturbing ER homeostasis.
The glycolytic enzyme phosphofructokinase-1 assembles into filaments
Phosphofructokinase-1 (PFK1) is an essential glycolysis enzyme as it catalyzes the step committing glucose to breakdown. Webb et al. show that the liver PFK1 isoform assembles into filaments in a tetramer- and substrate-dependent manner, providing insights into the spatial organization of isoform-specific glucose metabolism in cells.
Pink1 and Parkin regulate Drosophila intestinal stem cell proliferation during stress and aging
Recent findings indicate that stem cell metabolism plays an important role in the regulation of stem cell activity. Koehler et al. show that changes in mitochondrial homeostasis in vivo, via knockdown of Pink1 or Parkin, uncouple cellular and tissue aging in the intestine, in part through the induction of intestinal stem cell senescence.
The G protein–coupled receptor GPR31 promotes membrane association of KRAS
Mutant KRAS drives oncogenesis when associated with the plasma membrane. Fehrenbacher et al. identify GPR31, a G protein–coupled receptor, as a secretory pathway chaperone that guides the KRAS protein to the plasma membrane.
Article
A bifurcated signaling cascade of NIMA-related kinases controls distinct kinesins in anaphase
A signaling module of NIMA-related kinases (Neks) regulates two kinesins, Mklp2 and Kif14, to spatiotemporally coordinate their subcellular localizations and activities. This is important for faithful completion of cytokinesis and reveals novel mechanisms by which Neks regulate late mitosis.
Cell cycle–dependent spatial segregation of telomerase from sites of DNA damage
Telomerase can generate a novel telomere at a DNA break, with potentially lethal consequences for the cell. Ouenzar et al. reveal novel roles for Pif1, Rad52, and Siz1-dependent sumoylation in the spatial exclusion of telomerase from sites of DNA repair during the cell cycle.
Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage
Recent work implicated human Dicer in the DNA damage response. Burger et al. show that DNA damage induces phosphorylation of Dicer and promotes DNA repair in the nucleus.
Impaired spliceosomal UsnRNP assembly leads to Sm mRNA down-regulation and Sm protein degradation
Cellular spliceosomal UsnRNP assembly is assisted by the PRMT5 and SMN complexes. Prusty et al. demonstrate that perturbations in the assembly machinery of UsnRNPs trigger complex cellular responses, using ribosomes, exosome-mediated RNA degradation, and autophagy to prevent Sm protein aggregation.
Molecular model of fission yeast centrosome assembly determined by superresolution imaging
Bestul et al. use superresolution imaging to study fission yeast centrosome assembly. Their work reveals similarities and differences to duplication of the budding yeast centrosome, including involvement of Sfi1 in duplication and localization of SUN proteins to a ring-like structure.
Characterization of spindle pole body duplication reveals a regulatory role for nuclear pore complexes
The spindle pole body (SPB) of yeast organizes microtubules and is essential for chromosome segregation. The SPB duplicates once per cell cycle and subsequently becomes inserted into the nuclear envelope (NE). In this study, Rüthnick et al. describe how a nuclear pore complex becomes recruited to the new SPB during the duplication process. Disturbance of this recruitment process prevents insertion of the new SPB into the NE.
Mutation of the α-tubulin Tuba1a leads to straighter microtubules and perturbs neuronal migration
Mutation of α-tubulin isotypes is associated with cortical malformations. Belvindrah et al. show that Tuba1 mutation leads to impaired neuronal saltatory migration in vivo as a result of functional and structural microtubule defects. Comparative analyses of Tuba1a and Tuba8 in tubulin heterodimer structure and microtubule polymerization reveal an essential, noncompensated role for Tuba1a in the neuronal rostral migratory system.
CRMP-1 enhances EVL-mediated actin elongation to build lamellipodia and the actin cortex
CRMP proteins regulate the cytoskeleton, but the underlying mechanisms are poorly understood. Yu-Kemp et al. show that CRMP-1 helps Ena/VASP proteins elongate actin filaments to assemble actin networks that are necessary for the integrity of epithelial sheets.
Fusion, fission, and transport control asymmetric inheritance of mitochondria and protein aggregates
Asymmetric inheritance of cell organelles determines the fate of daughter cells. Böckler et al. use yeast as a model to demonstrate that the dynamics of mitochondrial fusion, fission, and transport determine partitioning of mitochondria and cytosolic protein aggregates, which is critical for rejuvenation of daughter cells.
Activity-dependent trafficking of lysosomes in dendrites and dendritic spines
How are membrane proteins in distal dendrites degraded by the lysosome? Goo et al. provide the first evidence that lysosomes are positioned locally at dendritic spines in an activity-dependent manner to facilitate the remodeling of synapses through local degradation.
A module for Rac temporal signal integration revealed with optogenetics
Dissecting the logic of individual signaling modules in complex networks can be challenging for cascades that exhibit feedback and redundancy. In this study, Graziano et al. take an optogenetics-based approach to identify and dissect a module that converts sustained PIP3 production to transient Rac activation in the neutrophil chemotaxis signaling network.
Regulation of RhoA by STAT3 coordinates glial scar formation
The transcription factor STAT3 is known to control glial scar formation, but the underlying mechanism is unknown. Renault-Mihara et al. show that inhibition of the small GTPase RhoA by STAT3 coordinates reactive astrocyte dynamics during glial scar formation.
Phosphoinositide-dependent enrichment of actin monomers in dendritic spines regulates synapse development and plasticity
Dendritic spines are small actin–based protrusions that serve as the postsynaptic platform for most excitatory synapses in the vertebrate brain. This study reveals a novel mechanism by which activity-dependent local enrichment of G-actin in dendritic spines regulates the remodeling of the actin cytoskeleton underlying synapse development and plasticity.
Novel function of a dynein light chain in actin assembly during clathrin-mediated endocytosis
Actin-capping protein is a key component of the actin cytoskeleton at sites of clathrin-mediated endocytosis. Farrell et al. show that a newly discovered component of the endocytic machinery belongs to the dynein light chain family and regulates the recruitment of actin-capping protein in a dynein motor–independent manner.
Autophagy gene FIP200 in neural progenitors non–cell autonomously controls differentiation by regulating microglia
Wang et al. show that deletion of autophagy gene FIP200 in neural stem cells (NSCs) leads to microglia infiltration into the subventricular zone (SVZ), inhibiting NSC differentiation non–cell autonomously in a p53-independent manner. Microglia infiltration into the SVZ is caused by increased chemokine expression in FIP200-null NSCs.
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