On the cover
Chiasson-MacKenzie et al. reveal that the tumor suppressor Merlin regulates the mechanical forces transduced between the apical cell cortex and cell–cell junctions, allowing the EGF receptor to be immobilized and inhibited when epithelial cells reach confluency. In Merlin-deficient Caco2 cells, increased cortical tension results in the coalescence of myosin IIA (red) and the distortion of intercellular boundaries, marked by F-actin (green).
Image © 2015 Chiasson-MacKenzie et al.
See page 391.
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In This Issue
Merlin casts its spell on the cortical cytoskeleton
The tumor suppressor Merlin/NF2 inhibits the proliferation of confluent cells by regulating tension at the apical cell cortex.
People & Ideas
Francesca Peri: Micromanaging the lives of microglia
Peri tracks the machinations of these guardians of healthy brains.
Spindle assembly checkpoint proteins regulate and monitor meiotic synapsis in C. elegans
In C. elegans, a meiotic checkpoint monitors synapsis between homologous chromosomes. Mad1, Mad2, and Bub3 are required for this checkpoint and negatively regulate synapsis, suggesting a possible role for these proteins in monitoring the stability of homologue pairing.
Stable intronic sequence RNAs have possible regulatory roles in Drosophila melanogaster
Stable intronic sequence RNAs (sisRNAs) are present in Drosophila melanogaster, and a sisRNA modulates its host gene expression by repressing a long noncoding RNA during embryogenesis.
ERO1-independent production of H2O2 within the endoplasmic reticulum fuels Prdx4-mediated oxidative protein folding
Tracking the kinetics of equilibration of H2O2 between compartments reveals unexpected isolation of the endoplasmic reticulum and hints at a hitherto unsuspected local source of peroxide.
A conserved family of proteins facilitates nascent lipid droplet budding from the ER
Visualization of nascent lipid droplets reveals that they form lens-like structures inside the ER membrane bilayer and that FIT proteins are necessary for lipid droplet protrusion toward the cytoplasm.
A conserved polybasic domain mediates plasma membrane targeting of Lgl and its regulation by hypoxia
The plasma membrane targeting of Lgl, a key polarity and tumor suppressor protein, is mediated by electrostatic interactions between a polybasic motif in Lgl and phospholipids on the plasma membrane, and this mechanism is regulated by hypoxia and aPKC-phosphorylation.
The periciliary ring in polarized epithelial cells is a hot spot for delivery of the apical protein gp135
The apical glycoprotein gp135 is delivered to a ring at the base of the primary cilium and subsequently moves in a radial fashion away from the cilium in a microtubule-dependent manner.
Nup132 modulates meiotic spindle attachment in fission yeast by regulating kinetochore assembly
The fission yeast nucleoporin Nup132 is required for timely assembly of outer kinetochore proteins during meiotic prophase and its depletion activates the spindle assembly checkpoint in meiosis I, suggesting a role in establishing monopolar spindle attachment through outer kinetochore reorganization at meiotic prophase.
The dynein cortical anchor Num1 activates dynein motility by relieving Pac1/LIS1-mediated inhibition
Upon offloading to Num1 cortical receptor sites in budding yeast, cytoplasmic dynein motility is switched “on” by a mechanism that likely involves Num1-mediated dissociation of the Pac1 inhibitor, a homologue of human LIS1.
Microtubule plus end–associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells
Herpes simplex virus particles that enter the cell do not randomly associate with microtubule filaments, but require plus end–binding proteins EB1, CLIP-170, and dynactin to initiate retrograde transport to the nucleus.
ARF6–JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
Interaction of plasma membrane ARF6 with JIP3/JIP4 effectors on MT1-MMP endosomes coordinates dynactin–dynein and kinesin-1 activity in a tug-of-war mechanism for endosome tubulation and MT1-MMP exocytosis to promote breast cancer cell invasion.
The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking
The HIV protein Vpr interacts with EB1, p150Glued, and dynein heavy chain and perturbs the centripetal movement of phagosomes and their maturation, resulting in impaired phagolysosome biogenesis, which is important for bacterial clearance and cytokine production.
Quality control of mitochondrial protein synthesis is required for membrane integrity and cell fitness
Impaired turnover of newly synthesized mitochondrial proteins of the oxidative phosphorylation complexes leads to protein over-accumulation in the inner mitochondrial membrane, thereby generating a stress that dissipates the mitochondrial membrane potential and therefore compromises organelle and cellular fitness.
NF2/Merlin mediates contact-dependent inhibition of EGFR mobility and internalization via cortical actomyosin
Merlin and Ezrin are central to a mechanism whereby mechanical forces transduced across the apical actomyosin cytoskeleton from cell junctions control the mobility and internalization of EGFR, providing novel insight into how cells inhibit mitogenic signaling in response to cell contact.
Synaptopodin couples epithelial contractility to α-actinin-4–dependent junction maturation
A novel tension-sensitive junctional protein, synaptopodin, can relay biophysical input from cellular actomyosin contractility to induce biochemical changes at cell–cell contacts, resulting in structural reorganization of the junctional complex and epithelial barrier maturation.
Rootletin organizes the ciliary rootlet to achieve neuron sensory function in Drosophila
Drosophila Rootletin organizes rootlets in sensory neurons, where it transmits multiple sensory inputs and maintains basal body cohesion, yet it is not required for cilium stability.
Molecular control of irreversible bistability during trypanosome developmental commitment
Phosphoproteomic and functional analysis of the developmental progression of Trypanosomes demonstrates that this transition shows bistability, with commitment to differentiation requiring new protein synthesis, and that the protein kinase NRK is a key regulator.
Coordinated niche-associated signals promote germline homeostasis in the Drosophila ovary
The Drosophila ovarian niche produces Hh molecules, which promote germline differentiation by suppressing niche-derived JAK/STAT signaling activity to maintain a low level of Dpp expression in escort cells.