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 form…

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 …

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 stab…

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…

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 presen…

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 …

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 b…

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 t…

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 …

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 …

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 biosigh…

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 a…

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 alon…

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 coor…

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 …

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 formatio…

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, mito…

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 prote…

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 enhan…

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-gene…

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 stab…

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…

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 f…

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 sur…

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 …

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.…

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 efficientl…

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. …

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 collec…

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, Arat…

P-cadherin provides the driving force for collective cell migration Collective cell migration is an important process in normal development, wound repair, and tumor metastasis. Plutoni et al. reveal that the cell adhesion molecule P-cadherin promotes collective cell migration via the small GTPase Cdc42, inducing cell polarization and increasing the…

How catastrophes help oocytes avoid disaster During meiosis, oocytes must attach homologous chromosomes to opposite spindle poles, but the cells take several hours to assemble a bipolar spindle. Gluszek et al. reveal that, in Drosophila oocytes, the microtubule catastrophe–promoting protein Sentin delays the formation of stable kinetochore–microtub…

Cells migrate on the crest of a wave Cells move through complex 3D environments in vivo, but studying 3D modes of migration in vitro remains a major challenge. Guetta-Terrier et al. examine the movement of cells along suspended nanofibers that mimic 3D fibrillar matrices and find that their migration is guided by fin-like protrusions that propagate…

CLIP-170 tips its hand in viral transport After entering a cell, many viruses move toward the nucleus by binding to the microtubule-based motor protein dynein. Jovasevic et al. reveal, however, that herpes simplex virus must first associate with the plus ends of microtubules in a process that requires the dynein accessory factor dynactin and the pl…

Maintaining the link between spindle and furrow position The cytokinetic cleavage furrow must be carefully aligned with the spindle midzone during asymmetric cell division. Pacquelet et al. discover a pathway that maintains the connection between spindle and furrow position in one-cell C. elegans embryos by inhibiting the accumulation of myosin at …

A conversation with Dick Tsien on moving from cardiac physiology to LTP in a half-dozen years, conformational signaling by channels, and being a physiologist in the UK when Hodgkin, Huxley, and Katz were all doing experiments Download PDF transcript Key words: cardiac physiology, neuroscience, LTP, calcium channels, N-type channels, Denis Noble, Al…

Pushing the envelope on spindle assembly During mitosis, numerous proteins accumulate around the mitotic spindle to help it assemble and segregate sister chromatids correctly. Schweizer et al. reveal that a membranous spindle envelope facilitates the accumulation of these proteins by excluding large organelles from the spindle region. This biosight…

A conversation with Henry Lester on nicotinic acetylcholine receptors, inside-out pharmacology, teaching MOOCs, and Richard Feynman’s thoughts about single-channel recording. Download PDF transcript Key words: nicotine, nAChR, nicotinic receptor, inside-out pharmacology, MOOCsBy Rockefeller University Press

Endocytosis brings closure to epithelial wounds Epithelial cells bordering a wound respond by forming two types of actin-based structure: dynamic membrane protrusions that help the cells crawl into the wound and/or seal it and an actomyosin cable that encircles the wound and closes it like a purse string. Matsubayashi et al. reveal that the endocyt…

A conversation with Don Bers on calcium signaling and compartmentation in cardiac myocytes. Download PDF transcript Key words: calcium, cardiomyocytes, cardiac contractility, calcium compartmentation, arrhythmias, CaM kinaseBy Rockefeller University Press

Interphase centrosomes flare up Centrosomes undergo dramatic changes in size and structure during the rapid cell cycles of early Drosophila embryos. Lerit et al. reveal that a scaffold formed by the proteins centrosomin and PLP is required to maintain the activity of interphase centrosomes, which is essential for nuclear spacing and proper chromoso…

Melanosomal cargoes BLOC'd off from alternate routes The BLOC-2 complex contains three subunits encoded by genes mutated in Hermansky-Pudlak syndrome, a disease caused by defects in the trafficking pathways that form melanosomes and other lysosome-related organelles. Dennis et al. reveal that the BLOC-2 complex promotes the delivery of melanosomal …

A conversation with Eduardo Ríos on post-Hodgkin thought, the voltage sensor in EC coupling, calcium sparks, and the university system in Uruguay. Download PDF transcript Key words: dihydropyridine receptor, ryanodine receptor, calcium sparks, cardiac muscle, skeletal muscle, calcium sparks, excitation-contraction coupling, calsequestrin…

Formin' actin at adherens junctions Actin assembly promotes the formation of intercellular adherens junctions, but the role of actin-nucleating formin proteins in this process remains unclear. Grikscheit et al. reveal that, in breast epithelial cells cultured in 3D, the formin FMNL2 stimulates junctional actin assembly downstream of the small GTPas…

A conversation with Paul Greengard on “hormonal” communication between nerve cells, the biochemical bases by which antidepressants work, and the Pearl Meister Greengard Prize for outstanding women in biomedical research. Download PDF transcript Key words: second messengers, protein phosphorylation, slow synaptic transmission, protein kinases, cGMP,…

A motif that helps myosin II-B lead from behind Myosin II-A and myosin II-B play distinct roles in establishing the front–back polarity of migrating mesenchymal cells. Juanes-Garcia et al. identify a short, serine-rich motif in the non-helical tail domain of myosin II-B that enables this isoform to form stable actomyosin bundles that define the cel…

A conversation with Chris Miller on channels, transporters, radical reductionism, and trusting your sense of scientific aesthetics. Download PDF Transcript Key words: ion channels, ion transporters, biophysics, ClC, chloride, fluoride, Fluc, lipid bilayersBy Rockefeller University Press

PAPC separates tissues at a Snail's pace Brachet's cleft separates the ectoderm and mesoderm of early Xenopus and zebrafish embryos. Luu et al. reveal that, in conjunction with the transcription factor Snail1, the protocadherin PAPC promotes tissue separation by down-regulating planar cell polarity proteins at the ectoderm-mesoderm boundary. This b…

A conversation with Richard Lewis on electrical resonance in hair cells, channels and signals in T cells, papayas in the lab, and following your nose. Download PDF transcript Key words: calcium, T cell, Hair cell, Papain, Orai, STIM, CRAC channelsBy Rockefeller University Press

Filopodia point the way for haptotaxis Migrating fibroblasts maintain or change their direction by branching off new lamellipodia from existing protrusions at the cell's leading edge. Johnson et al. reveal that filopodial protrusions initiate and orient these lamellipodia, helping fibroblasts navigate gradients of immobilized guidance cues. This bi…