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 environmen...
Jun 04, 2018•7 min
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 bio...
May 07, 2018•8 min
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 th...
Apr 02, 2018•6 min
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 inter...
Mar 05, 2018•7 min
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 senio...
Feb 05, 2018•7 min
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. fr...
Jan 02, 2018•7 min
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 p...
Dec 04, 2017•7 min
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...
Nov 06, 2017•9 min
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 reg...
Oct 02, 2017•7 min
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...
Sep 04, 2017•8 min
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...
Aug 07, 2017•7 min
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-a...
Jun 26, 2017•7 min
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 pa...
Jun 05, 2017•8 min
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 t...
May 01, 2017•8 min
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...
Apr 03, 2017•6 min
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, 2...
Mar 06, 2017•7 min
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 phosphorylati...
Feb 06, 2017•8 min
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 ...
Jan 02, 2017•8 min
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. fro...
Dec 19, 2016•8 min
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 Murugesa...
Nov 21, 2016•8 min
Retinal ganglion cells have a backup plan Retinal ganglion cells (RGCs) are born at the apical side of the retinal neuroepithelium before they translocate to the basal side and send out axons to form the optic nerve. Icha et al. reveal that, in the zebrafish retina, RGC translocation is expedited by basal process attachment and a population of stable microtubules. If necessary, however, RGCs can switch to a backup, multipolar migratory mode to ensure that they reach the basal lamina in time to s...
Oct 24, 2016•9 min
An iron hand controls endosome-mitochondria contacts In erythroid cells, endocytosed iron is directly transferred into mitochondria at dynamic endosome-mitochondria contacts. Das et al. reveal that this process also occurs in epithelial cells, and that the motility of endosomes, and the duration of their interactions with mitochondria, is modulated by intra-endosomal iron release from transferrin. This biosights episode presents the paper by Das et al. from the September 26th, 2016, issue of The...
Sep 26, 2016•6 min
Septins step in to promote macropinosome fusion After they are formed by the closure of membrane ruffles, macropinosomes mature by fusing with each other and with endosomes, before eventually delivering their fluid phase cargo to lysosomes. Dolat and Spiliotis reveal that septin filaments promote macropinosome maturation and lysosomal delivery by facilitating macropinosome/endosome fusion. This biosights episode presents the paper by Dolat and Spiliotis from the August 29th, 2016, issue of The J...
Aug 29, 2016•8 min
The midbody enables ciliogenesis Fibroblasts initiate ciliogenesis inside the cell, but polarized epithelial cells form a primary cilium at the apical cell surface through a mechanism that is largely uncharacterized. Bernabé-Rubio et al. reveal that, in polarized MDCK cells, a remnant of the cytokinetic midbody moves to the center of the apical surface, where it encounters the centrosome and enables cilium formation. This biosights episode presents the paper by Bernabé-Rubio et al. from the Augu...
Aug 01, 2016•7 min
Mobilizing mitochondria aids axon regeneration In mature neurons, the axonal transport of mitochondria is suppressed by the expression of the mitochondrial anchoring protein syntaphilin. Zhou et al. reveal that enhancing mitochondrial transport in mature neurons rescues energy deficits and facilitates axon regeneration after injury. This biosights episode presents the paper by Zhou et al. from the July 4th, 2016, issue of The Journal of Cell Biology and includes an interview with the paper's sen...
Jul 04, 2016•8 min
Neural crest cells stay within versican's confines Spatial confinement enhances collective cell migration in vitro, but whether it promotes collective migration in vivo is unclear. Szabó et al. reveal that the extracellular matrix protein versican confines neural crest cells to enhance their collective migration during Xenopus laevis embryogenesis. This biosights episode presents the paper by Szabó et al. from the June 6th, 2016, issue of The Journal of Cell Biology and includes an interview wit...
Jun 06, 2016•8 min
Surf's uptake! Exosomes ride filopodia into cells Exosomes are small, extracellular vesicles that transfer lipid, protein, and RNA cargoes between cells, but relatively little is known about how they are taken up and processed by their target cells. Heusermann et al. reveal that exosomes "surf" along recipient cell filopodia before being efficiently endocytosed and targeted to the endoplasmic reticulum. This biosights episode presents the paper by Heusermann et al. from the April 25, 2016, issue...
May 09, 2016•7 min
Sac1 works its contacts The plasma membrane phosphoinositide PI(4,5)P2 is derived from PI(4)P, whose levels are controlled by the essential lipid phosphatase Sac1. Sac1 is an integral ER membrane protein, but Dickson et al. reveal that it localizes to dynamic ER–plasma membrane contact sites to regulate plasma membrane PI(4)P and PI(4,5)P2 levels. This biosights episode presents the paper by Dickson et al. from the April 11th, 2016, issue of The Journal of Cell Biology and includes an interview ...
Apr 11, 2016•8 min
Fat2 whips fly eggs into shape During Drosophila oogenesis, the collective migration of egg chamber follicle cells drives the chambers' rotation and elongation. Squarr et al. reveal that the atypical cadherin Fat2 recruits the WAVE regulatory complex to tricellular junctions to induce the formation of whip-like actin protrusions that control collective migration and tissue rotation. This biosights episode presents the paper by Squarr et al. from the February 29th, 2016, issue of The Journal of C...
Mar 14, 2016•7 min
Chipping away at the problems of cardiac stem cell therapy Though stem cells transplanted into heart attack patients can develop into cardiomyocytes and integrate with undamaged host tissue, preclinical studies and clinical trials have only shown limited improvements in cardiac function. Using a simplified, in vitro, "muscle on-a-chip" system, Aratyn-Schaus et al. reveal that mechanical forces aren't transmitted efficiently between weaker, stem cell–derived cardiomyocytes and stronger, more matu...
Feb 15, 2016•6 min
