biosights: October 2, 2017

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.