Issues
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Cover Image
Cover Image
On the cover
An artistic view of Müller glial cells (green), which, MacDonald et al. reveal, act like springs to mechanically protect vertebrate retina. Image by Effigos AG.
Image © 2015 MacDonald et al.
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In This Issue
In Focus
Glycolytic cancer cells splice their way out of trouble
Cancer cells’ glycolytic phenotype drives alternative splicing of the proapoptotic protein Bnip3, producing a splice variant that protects against death.
People & Ideas
Nihal Altan-Bonnet: Tracking viruses that hijack membranes
Altan-Bonnet explores where membrane traffic meets health.
Feature
Report
Sam37 is crucial for formation of the mitochondrial TOM–SAM supercomplex, thereby promoting β-barrel biogenesis
Sam37 promotes biogenesis of mitochondrial proteins by linking outer membrane translocases into a supercomplex
ATP8B1-mediated spatial organization of Cdc42 signaling maintains singularity during enterocyte polarization
The disease-associated phospholipid flippase ATP8B1 decreases Cdc42 mobility at the apical membrane to ensure the formation of a single apical domain and to maintain healthy lumen architecture.
Reevaluating αE-catenin monomer and homodimer functions by characterizing E-cadherin/αE-catenin chimeras
Our results demonstrate that E-cadherin/αE-catenin chimeras homodimerize and do not mimic αE-catenin in the native CCC, and imply that both CCC-bound monomer and cytosolic homodimer αE-catenin are required for strong cell adhesion.
Müller glia provide essential tensile strength to the developing retina
When the formation of Müller glia is inhibited in the zebrafish retina, a major consequence is that the retina begins to rip apart due to a loss of the mechanical resilience that these glial cells provide to the neural tissue.
Article
PAR-4 and anillin regulate myosin to coordinate spindle and furrow position during asymmetric division
PAR-4/LKB-1, PIG-1/MELK, and the anillin ANI-1 inhibit the accumulation of myosin at the anterior cortex of asymmetrically dividing one-cell C. elegans embryos, thereby preventing myosin from uncoupling cytokinetic furrow and mitotic spindle positions.
PDK2-mediated alternative splicing switches Bnip3 from cell death to cell survival
In hypoxia, the survival property of cancer cells mediated by the glycolytic enzyme PDK2 is obligatorily linked to alternative splicing and generation of a novel isoform of death gene Bnip3, which suppresses mitochondrial injury and promotes survival.
Ubiquitin plays an atypical role in GPCR-induced p38 MAP kinase activation on endosomes
K63-linked ubiquitination of GPCRs mediated by the NEDD4-2 E3 ubiquitin ligase regulates recruitment of a TAB1–TAB2 complex on endosomes and stimulates p38 MAPK through a noncanonical pathway, which is critical for endothelial barrier disruption.
RUN and FYVE domain–containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4
Interleukin-4 boosts the capacity of dendritic cells to present endogenous antigens on MHC II and to resist bacterial infection through a mechanism shown to be partially dependent on RUFY4 expression.
mTOR and differential activation of mitochondria orchestrate neutrophil chemotaxis
Neutrophil chemotaxis is regulated by opposing autocrine purinergic signaling mechanisms, which are stimulated by mitochondrial ATP formation that is up-regulated via mTOR and P2Y2 receptors at the front and down-regulated via A2a receptors and cAMP/PKA signaling at the back of cells.
Integrins activate trimeric G proteins via the nonreceptor protein GIV/Girdin
GIV/Girdin, a nonreceptor GEF, directly links integrins to activation of trimeric G proteins to promote the acquisition of proinvasive traits in cancer cells.
PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation
Targeted deletion of PC7 and the related proprotein convertases Furin and Pace4, combined with live imaging of their activities, unmasks their overlapping and complementary functions in morula compaction and ICM formation in mouse blastocysts and in E-cadherin precursor processing.
Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels
Syndecans regulate members of the transient receptor potential family to control cytosolic calcium levels with impact on cell adhesion, junction formation, and neuronal guidance.
CRISP1 as a novel CatSper regulator that modulates sperm motility and orientation during fertilization
CRISP1 is expressed by cumulus cells and plays a role in fertilization by modulating sperm orientation, hyperactivation, and key Ca2+ channels in sperm.
A novel form of synaptic plasticity in field CA3 of hippocampus requires GPER1 activation and BDNF release
Estrogen gates metabotropic glutamate receptor–dependent long-term depression at mossy fiber–CA3 synapses through a mechanism involving GPER1-mediated BDNF release, mTOR-dependent protein synthesis, and proteasome activity.
Endothelial Msx1 transduces hemodynamic changes into an arteriogenic remodeling response
During peripheral arterial disease, MSX1 acts downstream of BMP–SMAD signaling to transduce the arterial shear stimulus into an arteriogenic remodeling response. MSX1 activates collateral endothelium into a proinflammatory state through ICAM1/VCAM1 up-regulation, resulting in increased leukocyte infiltration and collateral remodeling.
Tools
A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation
Inhibiting Src activity through genetic suppression or the small molecule inhibitor PP1 enhances the differentiation capacity of human pluripotent stem cells across all germ layers, and these improvements are preceded by activation of the retinoblastoma protein in the pluripotent cell cycle.
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