Issues

Alushin investigates the structural biology of biomechanical processes in the cytoskeleton.

Gonzalez-Rodriguez and Bunting preview work from the Sleckman laboratory describing a new function for the repair protein XLF in the protection of DNA replication fork stability.

King and Lusk preview work from Halfmann et al. that provides insight into the mechanisms that mediate the repair of nuclear envelope rupture.

Blow previews work from the Cook laboratory describing a defective DNA replication origin licensing checkpoint in cells re-entering the cell cycle from quiescence.

Del Signore and Rodal discuss work from Mondin et al. revealing a surprising collaboration between PTEN and PLCXD to restrict endosomal PtdIns(4,5)P₂ levels.

Broihier discusses the unexpected new role for Patronin in minus end growth of dendritic microtubules discovered by Feng et al.

Lock et al. offer a perspective on how the discovery of a new class of cell adhesion complex drives convergence of the integrin and clathrin fields.

Schulze et al. present an overview of the diverse functions of hepatocytes, including filtering blood, the secretion of bile, and lipid uptake and release.

Chen et al. show that XLF functions to limit fork reversal during DNA replication. H2AX prevents MRE11-dependent replication stress in XLF-deficient cells, suggesting that H2AX prevents the resection of regressed arms at reversed forks.

Dhatchinamoorthy et al. suggest the stoichiometry of outer submodules of the budding yeast kinetochore is strongly influenced by factors at the kinetochore–microtubule interface such as Fin1 and Dam1. Outer kinetochore stoichiometry is remarkably plastic and responsive to microtubule-proximal regulation.

Halfmann et al. describe a role for the protein BAF in nuclear envelope rupture repair. BAF recruits LEM-domain proteins and membranes to nuclear ruptures, yet surprisingly, ESCRT-III is not required to repair ruptures. These results provide new insight into the mechanisms of nuclear envelope repair.

Vertebrate cells assemble mitotic spindles through multiple pathways. It is shown that Augmin-dependent, noncentrosomal nucleation generates the vast majority of microtubules in metaphase spindles. This results in a strong directional bias of microtubule growth toward individual kinetochores.

Matson et al. find that human cells re-entering the cell cycle from quiescence have an impaired p53-dependent DNA replication origin licensing checkpoint and slow origin licensing. This combination makes every first S phase underlicensed and hypersensitive to replication stress.

Kodani et al. identify a role for the mammalian homologue of yeast SFI1 as a regulator of centriole duplication. They show that SFI1 localizes USP9X to the centrosome to stabilize the microcephaly protein STIL to promote centriole duplication.

This work reveals that the tumor suppressor PTEN acts through a PLC to reduce levels of endosomal PtdIns(4,5)P₂, its own enzymatic product. This pathway can be chemically activated to rescue OCRL1 depletion in several disease models of the Lowe syndrome, a rare multisystemic genetic disease.

Fourriere et al. demonstrate the existence of secretion hotspots juxtaposed to focal adhesions. Post-Golgi transport carriers use a subset of microtubules to reach focal adhesions. RAB6 acts as a general regulator of post-Golgi secretion and, together with ELKS, restricts protein secretion at focal adhesions.

It is unclear how a plethora of stimuli evoke differential cargo secretion from endothelial cells to produce stimulus-appropriate responses. Miteva et al. show that Rab46 integrates histamine signaling and Ca²⁺ signals to regulate selective cargo release from Weibel-Palade bodies.

BCR engagement enhances microtubule stability, which triggers the mobilization of Exo70 from the centrosome to the immune synapse. BCR engagement activates GEF-H1, which promotes exocyst assembly required for the docking and secretion of lysosomes, facilitating the extraction of surface-tethered antigens.

Using chemical genetics, we show that acute inhibition of otherwise rapamycin-insensitive TORC2 triggers a slow increase in plasma membrane tension that provokes snapping of the bonds between adaptor proteins and polymerizing actin filaments and ultimately the cessation of endocytosis in yeast.

Epithelial apicobasal polarity in Drosophila depends on the basolateral protein Scribble (Scrib), but the role of mammalian Scrib is unclear. Choi et al. now report that mammalian Scrib also mediates epithelial apicobasal polarity but this function is obscured by compensatory activity of other LAP proteins, Erbin and Lano.

Podocyte slit diaphragms are key components of the glomerular filtration barrier. Using Drosophila nephrocytes, Carrasco-Rando et al. propose a conserved role for Pyd/ZO-1 in triggering junctional remodeling leading to the formation of slit diaphragms.

Feng et al. describe persistent neuronal microtubule minus end growth that depends on the CAMSAP protein Patronin and is needed for dendritic minus-end-out polarity.

Synergism between myosin II contractility and cofilin activity modulates serotonin-dependent axon growth. Normally, cofilin-dependent decreases in actin density are compensated by increases in point contact density and traction force; however, myosin hyperactivation leads to catastrophic decreases in actin network density and neurite retraction.

Schwann cell–resident Ral GTPases foster radial sorting of axons in developing peripheral nerves and are involved in exocyst-dependent control of Schwann cell process extensions.

RalA and RalB are involved in cell migration and membrane dynamics. This study finds that ablation of RalGTPases impairs nerve regeneration and alters Schwann cell process formation; conversely, activation of RalGTPases enhancea Schwann cell process formation, migration, and axon myelination.

Proper regulation of NODAL signaling is fundamental for embryonic development and cancer. Osório et al. identify ISM1 as an extracellular antagonist of NODAL and uncover a novel molecular mechanism that negatively regulates NODAL signaling to control the asymmetric positioning of the heart in chick embryos.

Unicellular tubes, components of organs and capillaries, form intracellular lumens. Khan et al. report that a tensile triple intermediate-filament lattice, embedded between microfilaments and microtubules, tunnels the lumen through the single-cell C. elegans excretory canal and transforms concentric lumen expansion into lumen forward extension.

Tourrière et al. reported that G3BP1-S149 dephosphorylation promotes stress granule formation. Panas et al. show that constructs used to establish this conclusion contain additional mutations causing these phenotypes and that S149 phosphorylation status does not change upon stress.

In this issue, Panas et al. challenge the data published in the 2003 Tourrière et al. JCB paper on the role of G3BP phosphorylation in stress granule (SG) assembly. This reply addresses that letter and suggests that more work is needed to understand the role of this modification in SG formation.