biosights

Lymphatic exosomes help dendritic cells find their way

Under inflammatory conditions, antigen-presenting dendritic cells are attracted to lymphatic vessels by chemokines secreted from the basolateral surface of lymphatic endothelial cells. Brown et al. reveal that lymphatic endothelial cells also release exosomal vesicles that, by inducing the formation of cellular protrusions, improve the ability of dendritic cells to detect guidance cues and navigate their way through complex tissue environments. This biosights episode presents the paper by Brown et al. from the June 4th, 2018, issue of the Journal of Cell Biology and includes an interview with one of the paper's senior authors, Dontscho Kerjaschki (Medical University of Vienna). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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BBSome trains provide receptors a passage out of cilia

Many G protein–coupled receptors accumulate in the membrane of primary cilia and then exit this sensory organelle when their signaling pathway is activated. Ye et al. reveal that the BBSome complex facilitates the signal-dependent exit of GPCRs by moving them across a diffusion barrier located at the ciliary transition zone, although the receptors must then cross a second, periciliary diffusion barrier to completely exit the cilium. This biosights episode presents the paper by Ye et al. from the May 7th, 2018, issue of the Journal of Cell Biology and includes an interview with the paper's senior author, Maxence Nachury (University of California, San Francisco). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Dia1-dependent adhesions help epithelia branch out

The actin cytoskeleton and its regulators play key roles in the maturation and stabilization of focal adhesions but how adhesion maturation affects tissue morphogenesis is largely unknown. Fessenden et al. reveal that the actin-nucleating formin protein Dia1 promotes branching morphogenesis by stabilizing adhesions that are required for epithelial tissues to initiate invasion. This biosights episode presents the paper by Fessenden et al. from the April 2nd, 2018, issue of the Journal of Cell Biology and includes an interview with the paper's senior author, Margaret Gardel (University of Chicago). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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The nucleus comes through in the clutch

In addition to its roles in DNA replication and gene expression, the nucleus has an important physical impact on cellular behavior. Graham et al. reveal that, although the nucleus is dispensable for cell polarization and migration on 2D surfaces, it is crucial for regulating the cell's responses to mechanical cues. This biosights episode presents the paper by Graham et al. from the March 5th, 2018, issue of the Journal of Cell Biology and includes an interview with the paper's first author, David Graham, and its two senior authors, Jim Bear and Keith Burridge (University of North Carolina at Chapel Hill). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Cytotoxic T cells use Flower power

In order to efficiently kill multiple target cells, cytotoxic T lymphocytes must endocytose and recycle cytotoxic granule membrane components from the immunological synapse. Chang et al. reveal that a protein called Flower facilitates granule endocytosis in a calcium-dependent manner. This biosights episode presents the paper by Chang et al. from the February 5th, 2018, issue of the Journal of Cell Biology and includes an interview with one of the paper's senior authors, Jens Rettig (Saarland University, Saarbrücken, Germany). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Ring out your dead: MRCKα cleavage triggers epithelial extrusion

Dying epithelial cells are extruded from the tissue by a basal actomyosin ring formed in neighboring, healthy cells. Gagliardi et al. reveal that epithelial extrusion is also driven by actin rearrangements in the apoptotic cell, where cleavage of the kinase MRCKα induces the assembly of an apical actin ring that collapses the cell body and moves the dying cell upward. This biosights episode presents the paper by Gagliardi et al. from the January 2nd, 2018, issue of the Journal of Cell Biology and includes an interview with the paper's first author, Paolo Gagliardi (Candiolo Cancer Institute, Candiolo, Italy). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Adult neuroblasts DOCK into position

In the postnatal/adult brain, interneuron precursors, or neuroblasts, migrate along the rostral migratory stream by undergoing cycles of leading process extension followed by somal translocation. Nakamuta et al. reveal that the Rac/Cdc42 guanine nucleotide exchange factor DOCK7 coordinates this migratory cycle by regulating both Rac-dependent leading process extension and p116Rip-dependent actin assembly at the cell rear. This biosights episode presents the paper by Nakamuta et al. from the December 4th, 2017, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Linda Van Aelst (Cold Spring Harbor Laboratory, NY). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Cancer-associated fibroblasts lay the tracks for directional migration

Cancer-associated fibroblasts, or CAFs, regulate tumor progression by secreting chemokines and remodeling the extracellular matrix. Erdogan et al. reveal that the CAF-dependent alignment of fibronectin promotes directional cancer cell migration. This biosights episode presents the paper by Erdogan et al. from the November 6th, 2017, issue of The Journal of Cell Biology and includes an interview with two of the paper's authors, Begum Erdogan and Mingfang Ao (Vanderbilt University, Nashville, TN). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Drp1 cuts off mitophagy

Misfolded mitochondrial proteins can be eliminated by Parkin-dependent mitophagy but how this process selectively removes damaged mitochondrial regions is unclear. Burman et al. reveal that protein aggregates in the mitochondrial matrix trigger a local accumulation of Parkin on the mitochondrial outer membrane, and that the mitochondrial fission protein Drp1 segregates these domains to prevent Parkin accumulation from spreading and directing the elimination of healthy regions of the organelle. This biosights episode presents the paper by Burman et al. from the October 2nd, 2017, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Richard Youle (NINDS, NIH). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

Synaptic activity shifts dendritic lysosomes

Invading pathogens or other toxic agents can trigger the assembly of the inflammasome adaptor ASC into large, intracellular specks that activate caspase-1 to initiate a proinflammatory cell death called pyroptosis. Kuri et al. follow the dynamics of ASC speck formation in live zebrafish, revealing their lethal effects on epidermal keratinocytes and their subsequent engulfment and degradation by macrophages. This biosights episode presents the paper by Kuri et al. from the September 4th, 2017, issue of The Journal of Cell Biology and includes an interview with two of the paper's authors, Paola Kuri and Maria Leptin (EMBL). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

Synaptic activity shifts dendritic lysosomes

Lysosomes are known to exist in both the cell body and axon of neurons, but whether they also localize to dendrites is unclear. Goo et al. reveal that lysosomes do exist in dendrites and dendritic spines, and that their trafficking in this region of neurons is regulated by synaptic activity. This biosights episode presents the paper by Goo et al. from the August 7th, 2017, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Gentry Patrick (University of California, San Diego). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Myosins team up to help secretory granules integrate

Actomyosin contractility drives a variety of membrane remodeling events, including the integration of secretory granules into the apical plasma membrane after exocytosis. By visualizing granule integration in the salivary glands of live mice, Milberg et al. reveal that myosin IIA and myosin IIB act at different stages of the process and that the activation and assembly of these myosin isoforms into contractile filaments is regulated by the F-actin scaffold, which assembles on secretory granules and recruits myosin light chain kinase. This biosights episode presents the paper by Milberg et al. from the July 3rd, 2017, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Roberto Weigert (National Institutes of Health, Bethesda, MD). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Broken chromosomes stay on the safe side in mitosis

Unrepaired DNA double strand breaks can generate chromosome fragments that lack centromeres but, surprisingly, these acentric chromosomes can nevertheless segregate to spindle poles during mitosis. Karg et al. reveal that, in Drosophila melanogaster neuroblasts, acentric chromosomes segregate along interpolar microtubules at the spindle periphery that are organized by the chromokinesin motor protein Klp3a. This biosights episode presents the paper by Karg et al. from the June 5th, 2017, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, William Sullivan (University of California, Santa Cruz). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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The cell cortex makes use of plastin's connections

Cortical actomyosin contractility regulates a variety of morphogenetic processes at both the cellular and tissue-based levels. Ding et al. reveal that, in the Caenorhabditis elegans zygote, the actin cross-linking protein plastin optimizes connectivity within the cortical actomyosin network to coordinate large-scale contractile processes that drive cell polarization and cytokinesis. This biosights episode presents the paper by Ding et al. from the May 1st, 2017, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Ronen Zaidel-Bar (National University of Singapore). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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How Chlamydia help mitochondria keep it together

The obligate intracellular bacterium Chlamydia trachomatis must keep its host cell alive, even though it produces reactive oxygen species that expose the host cell to oxidative stress. Chowdhury et al. reveal that Chlamydia mitigates this oxidative stress by down-regulating the mitochondrial fission protein DRP1 via a microRNA- and p53-dependent pathway, thereby maintaining the mitochondrial network and ATP production to promote host cell survival and bacterial growth. This biosights episode presents the paper by Chowdhury et al. from the April 3rd, 2017, issue of The Journal of Cell Biology and includes an interview with two of the paper's authors, Suvagata Roy Chowdhury and Thomas Rudel (University of Würzburg, Würzburg, Germany). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Actin isoforms divide their responsibilities in motoneurons

Actin dynamics are crucial for axon growth and branching, but most studies have only focused on the role of β-actin. Moradi et al. reveal that α-, β-, and γ-actin have different functions in motoneuron axons; locally translated α-actin forms stable actin filaments that promote the formation of axonal branches, whereas β-actin regulates growth cone dynamics. This biosights episode presents the paper by Moradi et al. from the March 6th, 2017, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Michael Sendtner (University Hospital Würzburg, Würzburg, Germany). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Localizing mTORC2 activity

The mTORC2 complex regulates cell growth and proliferation by phosphorylating the protein kinase Akt, but where in the cell mTORC2 is active, and how growth factors direct its activity towards Akt, remains unclear. Ebner et al. use a novel reporter to show that endogenous mTORC2 activity localizes to plasma membrane, mitochondrial, and endosomal pools with distinct sensitivities to PI3 kinase and growth factor signaling, and that growth factors induce Akt phosphorylation by promoting Akt's recruitment to the plasma membrane. This biosights episode presents the paper by Ebner et al. from the February 6th, 2017, issue of The Journal of Cell Biology and includes an interview with two of the paper's authors, Michael Ebner and Ivan Yudushkin (Max F. Perutz Laboratories and Medical University of Vienna, Vienna, Austria). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Tumor cells feel the pressure after protease inhibition

Primary fibroblasts use a high pressure, “nuclear piston” mode of migration to move through highly cross-linked 3D extracellular matrices. Petrie et al. reveal that tumor cells with high levels of matrix metalloproteinase activity generally migrate by forming lamellipodia but, when their protease activity is inhibited, they can switch to the nuclear piston mechanism to force their nuclei through small gaps in the extracellular matrix. This biosights episode presents the paper by Petrie et al. from the January 2nd, 2017, issue of The Journal of Cell Biology and includes an interview with the paper’s senior author, Ryan Petrie (Drexel University, Philadelphia, PA). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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How NK cells avoid collateral damage

Before secreting their lytic granules to kill transformed or virally infected cells, natural killer cells converge these lysosome-related organelles around the microtubule-organizing center. Hsu et al. reveal that, by promoting the granules' directed secretion at the immunological synapse, convergence both enhances the efficiency of target cell killing and limits the death of healthy bystander cells. This biosights episode presents the paper by Hsu et al. from the December 19th, 2016, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Jordan Orange (Baylor College of Medicine, Houston, TX). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

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Formin’ arcs at the immunological synapse

When a T cell encounters an antigen-presenting cell, it dramatically reorganizes its cytoskeleton to form a specialized contact site called the immunological synapse. Murugesan et al. use superresolution microscopy to reveal that the medial region of the synapse contains a contractile network of formin-generated actomyosin arcs that sweep T cell receptor microclusters toward the center of the synapse. This biosights episode presents the paper by Murugesan et al. from the November 7th, 2016, issue of The Journal of Cell Biology and includes an interview with the paper’s senior author, John Hammer (NHLBI, Bethesda, MD). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.